LL-37

updated

LL-37 is the 37-residue C-terminal peptide of human cathelicidin, with no matching FDA application as of 9 October 2026. It has been given to people topically on ulcers and by injection into melanoma tumors; the largest trial, 148 patients with venous leg ulcers, found no significant healing improvement over placebo in the full population. No human study of injected, nebulized or orally dosed synthetic LL-37 was found.

Antimicrobial host defense peptide

  • openFDA Drugs@FDA queries for LL-37, cathelicidin and ropocamptide each returned no matching application on 9 October 2026. Ropocamptide is the INN assigned to the synthetic drug candidate.
  • In 34 people with hard-to-heal venous leg ulcers, healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL topical LL-37, and the 3.2 mg/mL group did not differ from placebo.
  • HEAL LL-37, a phase 2b trial in 148 patients with venous leg ulcers, did not identify any significant healing improvement versus placebo in the full study population.
  • In a diabetic foot ulcer trial, LL-37 cream raised a granulation measure at days 7 to 28 but did not significantly change IL-1 alpha, TNF-alpha or aerobic bacteria colonization versus placebo.
  • The one randomized infection trial, in 238 inpatients with COVID-19, used recombinant Lactococcus lactis expressing LL-37 by mouth, a genetically modified bacterium and not the synthetic peptide.
  • Two-thirds of patients with moderate-to-severe plaque psoriasis have T cells specific for LL37.

What is LL-37, and has anyone approved it?

LL-37 is the 37-residue C-terminal peptide of human cathelicidin (hCAP-18). Drugs@FDA queries for LL-37, cathelicidin and ropocamptide returned no matching application on 9 October 2026, so no LL-37 product is approved in the FDA record.

LL-37 is the 37-residue C-terminal peptide of human cathelicidin hCAP-18 (PubChem CID 16198951, C205H340N60O53, molecular weight 4493, CAS 154947-66-7). Listed synonyms include ropocamptide, which is the INN assigned to the synthetic drug candidate, plus Cap-18 and CAP18. Three different things carry the name and are kept separate on this page: the synthetic peptide, the endogenous peptide measured in saliva and serum, and a live bacterium engineered to express LL-37. The amino acid sequence is not given in the sources reviewed.

openFDA Drugs@FDA substance-name queries for LL-37, for cathelicidin and for ropocamptide each returned no matching application on 9 October 2026. There is no approved LL-37 product in the FDA record. This is a US-scoped statement, and approvals outside the United States are not covered.

PubChem: LL-37 identity and ropocamptide synonym

Chemical identity record

National Library of Medicine. PubChem compound record CID 16198951 (LL-37, human cathelicidin).

LL-37 is the 37-residue C-terminal peptide of human cathelicidin hCAP-18: PubChem CID 16198951, C205H340N60O53, molecular weight 4493, CAS 154947-66-7. Listed synonyms include ropocamptide, which is the INN assigned to the synthetic drug candidate, plus Cap-18 and CAP18.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined 37-residue peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The synthetic peptide, the endogenous peptide measured in saliva and serum, and a live bacterium engineered to express LL-37 are three different things and are kept separate on this page.

Read the original source
Drugs@FDA queries, 9 October 2026: no matching application

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA substance-name queries for LL-37, for cathelicidin and for ropocamptide, run on 9 October 2026.

openFDA Drugs@FDA substance-name queries for LL-37, for cathelicidin and for ropocamptide each returned no matching application on 9 October 2026. There is no approved LL-37 product in the FDA record.

Participants / model
Regulator database, not a population
Treatment
Exact substance-name searches
Follow-up
Searches run on 9 October 2026
Study design
FDA API query
Funding
not stated in the source

This is a US-scoped statement.

Read the original source

What have studies of LL-37 in people found?

LL-37 has been given to people topically on ulcers and by injection into melanoma tumors. In 34 people with venous leg ulcers, healing rate constants were about sixfold and threefold higher than placebo at two concentrations, but the 148-patient phase 2b trial found no significant healing improvement in the full population. The melanoma record covers 3 participants.

The first-in-man wound trial enrolled 34 participants with hard-to-heal venous leg ulcers. They went through a 3-week open-label run-in on placebo, then a 4-week randomized double-blind phase with twice-weekly topical applications of LL-37 at 0.5, 1.6 or 3.2 mg/mL or placebo, then 4 weeks of follow-up. Healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL (p=0.003 and p=0.088). Mean ulcer area fell 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. The 3.2 mg/mL group did not differ from placebo, so the dose-response is inverted at the top concentration. No local or systemic safety concerns were reported.

The larger wound trial missed its endpoint. HEAL LL-37 was a phase 2b double-blind randomized placebo-controlled study in 148 patients with hard-to-heal venous leg ulcers, in three arms (LL-37 0.5 mg/mL, LL-37 1.6 mg/mL, placebo) in combination with compression therapy. Patients had a mean age of 67.6 years, median ulcer duration 20.3 months and mean wound size 11.6 cm2 at randomization. The efficacy analysis on the full study population did not identify any significant improvement in healing versus placebo. A post hoc analysis found significant improvement in the subgroup with target wounds of at least 10 cm2. The drug was well tolerated and safe at both concentrations. The post hoc subgroup is hypothesis-generating, not a result.

In a randomized double-blind controlled trial run in Jakarta from January 2020 to June 2021, subjects applied LL-37 cream or placebo cream twice weekly for 4 weeks on diabetic foot ulcers with mild infection. The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. The cream improved a granulation measure and did not lower cytokines or bacterial counts. The registry record NCT04098562 lists a planned enrollment of 40, a start in October 2019, completion in January 2020, an overall status of unknown and no posted results.

The only registered study that injected LL-37 into people was NCT02225366, a phase 1/2 study at a single US cancer center. It gave weekly intratumoral injections of LL37 into cutaneous or subcutaneous melanoma tumors at least 1 cm in diameter for up to 8 weeks, starting at 250 mcg per tumor with a second cohort at 500 mcg per tumor. Actual enrollment was 4, and posted results cover 3 participants (2 in cohort 1, 1 in cohort 2). The study completed on 24 November 2020. This is a 3-participant dose-finding record and cannot support an efficacy claim in any population.

Every human study of the synthetic peptide used a topical or intratumoral route on a local target. The topical concentrations were applied to open wounds and are not systemic doses.

Venous leg ulcers: 34 participants, healing rate sixfold and threefold at 0.5 and 1.6 mg/mL

Randomized controlled trial

Grönberg A et al. Wound Repair Regen. 2014;22(5):613-21. PMID 25041740.

Healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL (p=0.003 and p=0.088). Mean ulcer area fell 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. The 3.2 mg/mL group did not differ from placebo, so the dose-response is inverted at the top concentration. No local or systemic safety concerns were reported.

Participants / model
34 adults with hard-to-heal venous leg ulcers
Treatment
Topical LL-37 at 0.5, 1.6 or 3.2 mg/mL, or placebo, applied twice weekly
Follow-up
3-week open-label placebo run-in, 4-week randomized double-blind phase, then 4 weeks of follow-up
Study design
Randomized double-blind placebo-controlled first-in-man trial with an open-label run-in
Funding
not stated in the source

The concentrations were applied to an open wound and are not systemic doses.

Read the original source
HEAL LL-37: 148 patients, phase 2b, no significant healing improvement in the full population

Randomized controlled trial

Mahlapuu M et al. Wound Repair Regen. 2021;29(6):938-950. PMID 34687253.

The efficacy analysis on the full study population did not identify any significant improvement in healing versus placebo. A post hoc analysis found significant improvement in the subgroup with target wounds of at least 10 cm2. The drug was well tolerated and safe at both concentrations.

Participants / model
148 patients with hard-to-heal venous leg ulcers (mean age 67.6 years, median ulcer duration 20.3 months, mean wound size 11.6 cm2 at randomization)
Treatment
Topical LL-37 0.5 mg/mL, LL-37 1.6 mg/mL or placebo, in combination with compression therapy
Follow-up
not stated in the source
Study design
Phase 2b double-blind randomized placebo-controlled trial, three arms
Funding
not stated in the source

The post hoc subgroup is hypothesis-generating, not a result.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source
Registry NCT04098562: phase 2, planned enrollment 40, status unknown, no posted results

Trial registry record

ClinicalTrials.gov. NCT04098562, phase 2 study of LL-37 cream in diabetic foot ulcers.

NCT04098562 is a phase 2 study of LL-37 cream in diabetic foot ulcers with a planned enrollment of 40, a start in October 2019 and completion in January 2020, recorded with an overall status of unknown and no posted results.

Participants / model
Patients with diabetic foot ulcer
Treatment
Topical LL-37 cream, 0.5 mg/mL
Follow-up
Registered October 2019 to January 2020
Study design
Registered healing, bacteriology and inflammation outcomes; no posted results
Funding
not stated in the source

The registration supports that the study existed; the published report supplies the result.

Read the original source
Registry NCT02225366: 4 enrolled, 3 with posted results, 0 serious adverse events

Trial registry record

ClinicalTrials.gov. NCT02225366, phase 1/2 study of intratumoral LL37 in cutaneous or subcutaneous melanoma, with posted results.

NCT02225366, a phase 1/2 study at a single US cancer center, gave weekly intratumoral injections of LL37 into cutaneous or subcutaneous melanoma tumors at least 1 cm in diameter for up to 8 weeks, starting at 250 mcg per tumor with a second cohort at 500 mcg per tumor. Actual enrollment was 4; posted results cover 3 participants (2 in cohort 1, 1 in cohort 2). The study completed on 24 November 2020. Posted safety data report 0 deaths and 0 serious adverse events, with other adverse events in 2 of 2 participants in cohort 1 and in the cohort 2 participant; 1 participant discontinued for lack of efficacy.

Participants / model
4 enrolled patients with melanoma, 3 with posted results
Treatment
Intratumoral LL37 injection, 250 or 500 mcg per tumor weekly
Follow-up
Up to 8 weeks; study completed 24 November 2020
Study design
Phase 1/2 dose-finding study with posted results; outcomes were optimal biological dose by toxicity, antitumor immune response and adverse events
Funding
not stated in the source

The only registered study that injected LL-37 into people. A 3-participant dose-finding record cannot support an efficacy claim in any population.

Read the original source

What did the one infection trial test?

It tested recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium taken by mouth, not the synthetic peptide. In 238 adult inpatients with COVID-19, viral RNA cleared in 9.80 versus 14.04 days on placebo when started within 6 days of case confirmation. It was open-label at one center and measured viral RNA clearance, not symptoms, hospitalization or death.

The one randomized infection trial used a live bacterium, not the peptide. An open-label randomized placebo-controlled single-center study in 238 adult inpatients tested recombinant Lactococcus lactis expressing LL-37 against the Omicron BA.5.1.3 variant of SARS-CoV-2. When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo (p<0.01), with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

The product is a genetically modified Lactococcus lactis expressing LL-37, given by mouth. It is not a synthetic LL-37 peptide and is not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Infection trial: 238 inpatients, genetically modified Lactococcus lactis by mouth, viral RNA clearance 9.80 versus 14.04 days

Randomized controlled trial

Zhao Y et al. J Med Virol. 2023;95(8):e29035. PMID 37605995.

When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo, p<0.01, with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

Participants / model
238 adult inpatients with COVID-19 (Omicron BA.5.1.3 variant)
Treatment
Oral recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium
Follow-up
not stated in the source
Study design
Open-label randomized placebo-controlled single-center study
Funding
not stated in the source

The product is a genetically modified Lactococcus lactis expressing LL-37 given by mouth, not a synthetic LL-37 peptide and not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Read the original source

Does LL-37 kill germs in the lab, and does that carry over to infection?

In test-tube assays, LL-37 had MICs under 10 micrograms/mL against several bacteria in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans resisted at 100 mM NaCl, and Burkholderia cepacia resisted at either salt concentration. These are in vitro results and do not show that LL-37 clears an infection in a person.

In radial diffusion and broth microdilution assays, LL-37 showed considerable activity (MIC under 10 micrograms/mL) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci even in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at 100 mM NaCl but susceptible in low-salt media. Burkholderia cepacia was resistant at either salt concentration. LL-37 bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes. These are test-tube MICs at defined salt concentrations, not evidence that LL-37 clears an infection in a person.

The LL-37 plus VIP pairing has one record, and it is a test tube. Bactericidal assays against Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans and Staphylococcus aureus found that the killing effect of vasoactive intestinal peptide or orexin B alone was detectable at low NaCl but attenuated at physiological 150 mM NaCl, and that adding LL-37 restored it. That is an additive in vitro bactericidal observation in four bacterial species. No human or animal study of the combination was located.

The one human wound trial that counted bacteria, the diabetic foot ulcer cream trial, found no significant difference between LL-37 and placebo in the fall in aerobic bacteria colonization.

Test-tube MICs: activity at 100 mM NaCl against some organisms, resistance in others

Cell study

Turner J et al. Antimicrob Agents Chemother. 1998;42(9):2206-14. PMID 9736536.

In radial diffusion and broth microdilution assays, LL-37 showed considerable activity (MIC under 10 micrograms/mL) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci even in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at 100 mM NaCl but susceptible in low-salt media. Burkholderia cepacia was resistant at either salt concentration. LL-37 bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes.

Participants / model
Bacterial and fungal isolates in vitro
Treatment
LL-37 in radial diffusion and broth microdilution assays
Follow-up
not stated in the source
Study design
In vitro mechanistic study
Funding
not stated in the source

These are test-tube MICs at defined salt concentrations, not evidence that LL-37 clears an infection in a person.

Read the original source
LL-37 with VIP: one test-tube bactericidal assay in four bacterial species

Cell study

Ohta K et al. J Neuroimmunol. 2011;233(1-2):37-45. PMID 21176972.

Bactericidal assays against Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans and Staphylococcus aureus found that the killing effect of vasoactive intestinal peptide or orexin B alone was detectable at low NaCl but attenuated at physiological 150 mM NaCl, and that adding LL-37 restored it. That is an additive in vitro bactericidal observation in four bacterial species.

Participants / model
Bacterial cultures in vitro
Treatment
LL-37 with VIP or orexin B in buffer
Follow-up
not stated in the source
Study design
In vitro bactericidal assays at varying NaCl
Funding
not stated in the source

No human or animal study of the LL-37 and VIP combination was located.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source

Do the sellers' claims about infection, immunity, mucosal repair and a KPV stack hold up?

Not on the records reviewed. Antimicrobial coverage rests on test-tube MICs, cytokine control is contradicted by the one human trial that measured cytokines, and respiratory and gut repair, systemic use and the KPV pairing have no human study of synthetic LL-37. A ClinicalTrials.gov search on 9 October 2026 found only two studies giving LL-37 to people as a drug.

Sellers say LL-37 supports acute infection, modulates immunity, repairs respiratory and gut mucosa, provides antimicrobial coverage, and is stacked with KPV and VIP for cytokine control.

Antimicrobial coverage is an in vitro MIC panel that loses several organisms at 100 mM NaCl, and the one human trial that counted bacteria found no significant reduction. Cytokine control is contradicted by that same trial, in which IL-1 alpha and TNF-alpha rose in both arms. Respiratory and gut mucosal repair have no human administration study. Acute infection support rests on one open-label single-center trial of a genetically modified Lactococcus lactis taken by mouth, which is a different product from synthetic peptide. The VIP pairing is one in vitro bactericidal assay in four bacterial species, and the KPV pairing has no study: a PubMed search for LL-37 with KPV returned 1 record, a 2025 review of host defense peptides in inflammatory bowel disease, not a combination study.

A ClinicalTrials.gov intervention-scoped search for LL-37 returned 20 records on 9 October 2026. Only two gave LL-37 to people as a drug: the topical diabetic foot ulcer cream and the intratumoral melanoma study. The other 18 measured endogenous cathelicidin as a biomarker in saliva, gingival fluid or serum, or tested vitamin D and mouthwashes. A PubMed search the same day for LL-37 or ropocamptide with intravenous, subcutaneous, intramuscular, inhaled, nebulized or intranasal routes, limited to human records, returned 40 records, none of which administered LL-37 systemically or by inhalation to people.

There is no human evidence for injected, nebulized or orally dosed synthetic LL-37 for infection, respiratory repair or gut repair, and none for the KPV stack.

Searches, 9 October 2026: 2 of 20 registry records gave LL-37 as a drug; no systemic or inhaled human use

PubMed search record

PubMed search run on 9 October 2026: (LL-37 OR ropocamptide) AND (intravenous OR subcutaneous OR intramuscular OR inhaled OR nebulized OR intranasal), humans MeSH term, 40 records. ClinicalTrials.gov intervention-scoped search for LL-37, 20 records, and a PubMed search for LL-37 with KPV, 1 record, run the same day.

A ClinicalTrials.gov intervention-scoped search for LL-37 returned 20 records. Only two gave LL-37 to people as a drug: the topical diabetic foot ulcer cream and the intratumoral melanoma study. The other 18 measured endogenous cathelicidin as a biomarker in saliva, gingival fluid or serum, or tested vitamin D and mouthwashes. A PubMed search for LL-37 or ropocamptide with intravenous, subcutaneous, intramuscular, inhaled, nebulized or intranasal routes, limited to human records, returned 40 records, none of which administered LL-37 systemically or by inhalation to people. A PubMed search for LL-37 with KPV returned 1 record, a 2025 review of host defense peptides in inflammatory bowel disease, not a combination study.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source
Test-tube MICs: activity at 100 mM NaCl against some organisms, resistance in others

Cell study

Turner J et al. Antimicrob Agents Chemother. 1998;42(9):2206-14. PMID 9736536.

In radial diffusion and broth microdilution assays, LL-37 showed considerable activity (MIC under 10 micrograms/mL) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci even in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at 100 mM NaCl but susceptible in low-salt media. Burkholderia cepacia was resistant at either salt concentration. LL-37 bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes.

Participants / model
Bacterial and fungal isolates in vitro
Treatment
LL-37 in radial diffusion and broth microdilution assays
Follow-up
not stated in the source
Study design
In vitro mechanistic study
Funding
not stated in the source

These are test-tube MICs at defined salt concentrations, not evidence that LL-37 clears an infection in a person.

Read the original source
Infection trial: 238 inpatients, genetically modified Lactococcus lactis by mouth, viral RNA clearance 9.80 versus 14.04 days

Randomized controlled trial

Zhao Y et al. J Med Virol. 2023;95(8):e29035. PMID 37605995.

When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo, p<0.01, with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

Participants / model
238 adult inpatients with COVID-19 (Omicron BA.5.1.3 variant)
Treatment
Oral recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium
Follow-up
not stated in the source
Study design
Open-label randomized placebo-controlled single-center study
Funding
not stated in the source

The product is a genetically modified Lactococcus lactis expressing LL-37 given by mouth, not a synthetic LL-37 peptide and not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Read the original source
LL-37 with VIP: one test-tube bactericidal assay in four bacterial species

Cell study

Ohta K et al. J Neuroimmunol. 2011;233(1-2):37-45. PMID 21176972.

Bactericidal assays against Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans and Staphylococcus aureus found that the killing effect of vasoactive intestinal peptide or orexin B alone was detectable at low NaCl but attenuated at physiological 150 mM NaCl, and that adding LL-37 restored it. That is an additive in vitro bactericidal observation in four bacterial species.

Participants / model
Bacterial cultures in vitro
Treatment
LL-37 with VIP or orexin B in buffer
Follow-up
not stated in the source
Study design
In vitro bactericidal assays at varying NaCl
Funding
not stated in the source

No human or animal study of the LL-37 and VIP combination was located.

Read the original source

How does LL-37 work, and what is known about its fate in the body?

LL-37 is an endogenous human peptide. In test-tube assays it bound bacterial lipopolysaccharide with high affinity and permeabilized E. coli membranes. No pharmacokinetic values for synthetic LL-37 appear in the sources reviewed.

LL-37 is the 37-residue C-terminal peptide of human cathelicidin hCAP-18, an endogenous peptide measured in saliva and serum. In vitro it bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes.

In the diabetic foot ulcer trial, baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein). The sources reviewed do not establish how the cream produced the granulation change.

No half-life, Tmax, absorption or clearance data for synthetic LL-37 are given in the sources reviewed.

PubChem: LL-37 identity and ropocamptide synonym

Chemical identity record

National Library of Medicine. PubChem compound record CID 16198951 (LL-37, human cathelicidin).

LL-37 is the 37-residue C-terminal peptide of human cathelicidin hCAP-18: PubChem CID 16198951, C205H340N60O53, molecular weight 4493, CAS 154947-66-7. Listed synonyms include ropocamptide, which is the INN assigned to the synthetic drug candidate, plus Cap-18 and CAP18.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined 37-residue peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The synthetic peptide, the endogenous peptide measured in saliva and serum, and a live bacterium engineered to express LL-37 are three different things and are kept separate on this page.

Read the original source
Test-tube MICs: activity at 100 mM NaCl against some organisms, resistance in others

Cell study

Turner J et al. Antimicrob Agents Chemother. 1998;42(9):2206-14. PMID 9736536.

In radial diffusion and broth microdilution assays, LL-37 showed considerable activity (MIC under 10 micrograms/mL) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci even in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at 100 mM NaCl but susceptible in low-salt media. Burkholderia cepacia was resistant at either salt concentration. LL-37 bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes.

Participants / model
Bacterial and fungal isolates in vitro
Treatment
LL-37 in radial diffusion and broth microdilution assays
Follow-up
not stated in the source
Study design
In vitro mechanistic study
Funding
not stated in the source

These are test-tube MICs at defined salt concentrations, not evidence that LL-37 clears an infection in a person.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source

What safety signals do the studies show?

LL37 is a T-cell autoantigen in psoriasis: two-thirds of patients with moderate-to-severe plaque psoriasis have LL37-specific T cells that track with disease activity. The wound trials reported no safety concerns and the melanoma record posted 0 deaths and 0 serious adverse events in 3 participants, but none covers systemic use.

LL37 is a T-cell autoantigen in psoriasis. Two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4+ and/or CD8+ T cells specific for LL37. Those T cells produce IFN-gamma and, for the CD4+ cells, Th17 cytokines, they can infiltrate lesional skin, and their presence in blood correlates significantly with disease activity. LL-37 is therefore not an inert molecule: it is a self-antigen that a substantial fraction of people with an inflammatory skin disease already have T cells against.

The first-in-man venous leg ulcer trial reported no local or systemic safety concerns, and HEAL LL-37 reported that the drug was well tolerated and safe at both concentrations. Both were topical studies on wounds.

In the melanoma record, posted safety data report 0 deaths and 0 serious adverse events, with other adverse events in 2 of 2 participants in cohort 1 and in the cohort 2 participant; 1 participant discontinued for lack of efficacy. That is 3 participants with posted results. The recombinant Lactococcus lactis trial observed no severe adverse events in 238 inpatients.

No safety data for injected, inhaled or orally dosed synthetic LL-37 in people were found.

Psoriasis: two-thirds of patients have LL37-specific T cells that track disease activity

Human study

Lande R et al. Nat Commun. 2014;5:5621. PMID 25470744.

Two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4+ and/or CD8+ T cells specific for LL37. Those T cells produce IFN-gamma and, for the CD4+ cells, Th17 cytokines, they can infiltrate lesional skin, and their presence in blood correlates significantly with disease activity.

Participants / model
Patients with moderate-to-severe plaque psoriasis
Treatment
Endogenous and synthetic LL37 used as antigen in T-cell assays
Follow-up
not stated in the source
Study design
Clinical and mechanistic study of T-cell frequency, cytokine production and correlation with disease activity
Funding
not stated in the source

LL37 is a T-cell autoantigen in psoriasis. It is a self-antigen that a substantial fraction of people with this inflammatory skin disease already have T cells against.

Read the original source
Venous leg ulcers: 34 participants, healing rate sixfold and threefold at 0.5 and 1.6 mg/mL

Randomized controlled trial

Grönberg A et al. Wound Repair Regen. 2014;22(5):613-21. PMID 25041740.

Healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL (p=0.003 and p=0.088). Mean ulcer area fell 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. The 3.2 mg/mL group did not differ from placebo, so the dose-response is inverted at the top concentration. No local or systemic safety concerns were reported.

Participants / model
34 adults with hard-to-heal venous leg ulcers
Treatment
Topical LL-37 at 0.5, 1.6 or 3.2 mg/mL, or placebo, applied twice weekly
Follow-up
3-week open-label placebo run-in, 4-week randomized double-blind phase, then 4 weeks of follow-up
Study design
Randomized double-blind placebo-controlled first-in-man trial with an open-label run-in
Funding
not stated in the source

The concentrations were applied to an open wound and are not systemic doses.

Read the original source
HEAL LL-37: 148 patients, phase 2b, no significant healing improvement in the full population

Randomized controlled trial

Mahlapuu M et al. Wound Repair Regen. 2021;29(6):938-950. PMID 34687253.

The efficacy analysis on the full study population did not identify any significant improvement in healing versus placebo. A post hoc analysis found significant improvement in the subgroup with target wounds of at least 10 cm2. The drug was well tolerated and safe at both concentrations.

Participants / model
148 patients with hard-to-heal venous leg ulcers (mean age 67.6 years, median ulcer duration 20.3 months, mean wound size 11.6 cm2 at randomization)
Treatment
Topical LL-37 0.5 mg/mL, LL-37 1.6 mg/mL or placebo, in combination with compression therapy
Follow-up
not stated in the source
Study design
Phase 2b double-blind randomized placebo-controlled trial, three arms
Funding
not stated in the source

The post hoc subgroup is hypothesis-generating, not a result.

Read the original source
Registry NCT02225366: 4 enrolled, 3 with posted results, 0 serious adverse events

Trial registry record

ClinicalTrials.gov. NCT02225366, phase 1/2 study of intratumoral LL37 in cutaneous or subcutaneous melanoma, with posted results.

NCT02225366, a phase 1/2 study at a single US cancer center, gave weekly intratumoral injections of LL37 into cutaneous or subcutaneous melanoma tumors at least 1 cm in diameter for up to 8 weeks, starting at 250 mcg per tumor with a second cohort at 500 mcg per tumor. Actual enrollment was 4; posted results cover 3 participants (2 in cohort 1, 1 in cohort 2). The study completed on 24 November 2020. Posted safety data report 0 deaths and 0 serious adverse events, with other adverse events in 2 of 2 participants in cohort 1 and in the cohort 2 participant; 1 participant discontinued for lack of efficacy.

Participants / model
4 enrolled patients with melanoma, 3 with posted results
Treatment
Intratumoral LL37 injection, 250 or 500 mcg per tumor weekly
Follow-up
Up to 8 weeks; study completed 24 November 2020
Study design
Phase 1/2 dose-finding study with posted results; outcomes were optimal biological dose by toxicity, antitumor immune response and adverse events
Funding
not stated in the source

The only registered study that injected LL-37 into people. A 3-participant dose-finding record cannot support an efficacy claim in any population.

Read the original source
Infection trial: 238 inpatients, genetically modified Lactococcus lactis by mouth, viral RNA clearance 9.80 versus 14.04 days

Randomized controlled trial

Zhao Y et al. J Med Virol. 2023;95(8):e29035. PMID 37605995.

When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo, p<0.01, with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

Participants / model
238 adult inpatients with COVID-19 (Omicron BA.5.1.3 variant)
Treatment
Oral recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium
Follow-up
not stated in the source
Study design
Open-label randomized placebo-controlled single-center study
Funding
not stated in the source

The product is a genetically modified Lactococcus lactis expressing LL-37 given by mouth, not a synthetic LL-37 peptide and not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Read the original source
Searches, 9 October 2026: 2 of 20 registry records gave LL-37 as a drug; no systemic or inhaled human use

PubMed search record

PubMed search run on 9 October 2026: (LL-37 OR ropocamptide) AND (intravenous OR subcutaneous OR intramuscular OR inhaled OR nebulized OR intranasal), humans MeSH term, 40 records. ClinicalTrials.gov intervention-scoped search for LL-37, 20 records, and a PubMed search for LL-37 with KPV, 1 record, run the same day.

A ClinicalTrials.gov intervention-scoped search for LL-37 returned 20 records. Only two gave LL-37 to people as a drug: the topical diabetic foot ulcer cream and the intratumoral melanoma study. The other 18 measured endogenous cathelicidin as a biomarker in saliva, gingival fluid or serum, or tested vitamin D and mouthwashes. A PubMed search for LL-37 or ropocamptide with intravenous, subcutaneous, intramuscular, inhaled, nebulized or intranasal routes, limited to human records, returned 40 records, none of which administered LL-37 systemically or by inhalation to people. A PubMed search for LL-37 with KPV returned 1 record, a 2025 review of host defense peptides in inflammatory bowel disease, not a combination study.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Why does LL-37 sit in C tier?

LL-37 is a real human peptide with a drug development history, but its human outcome data are thin and partly negative: the largest trial, 148 patients, found no significant healing improvement in the full population. The sellers' infection, mucosal repair and KPV claims have no human study of synthetic LL-37 behind them.

LL-37 is a real endogenous peptide with a development history under the INN ropocamptide, and it has been given to people in four studies of the synthetic peptide: two venous leg ulcer trials, one diabetic foot ulcer trial and one 4-patient melanoma dose-finding study. Every one used a topical or intratumoral route on a local target.

The largest of them, 148 patients, found no significant improvement over placebo on its efficacy analysis in the full population, and recovered only a post hoc subgroup. That is a plausible mechanism with thin and partly negative outcome data.

The sellers' claims do not hold on these records. Antimicrobial coverage is an in vitro MIC panel that loses several organisms at 100 mM NaCl. Cytokine control is contradicted by the diabetic foot ulcer trial, where IL-1 alpha and TNF-alpha rose in both arms. Respiratory and gut mucosal repair have no human administration study, the one infection trial used a genetically modified Lactococcus lactis taken by mouth, and the VIP pairing is one test-tube assay.

HEAL LL-37: 148 patients, phase 2b, no significant healing improvement in the full population

Randomized controlled trial

Mahlapuu M et al. Wound Repair Regen. 2021;29(6):938-950. PMID 34687253.

The efficacy analysis on the full study population did not identify any significant improvement in healing versus placebo. A post hoc analysis found significant improvement in the subgroup with target wounds of at least 10 cm2. The drug was well tolerated and safe at both concentrations.

Participants / model
148 patients with hard-to-heal venous leg ulcers (mean age 67.6 years, median ulcer duration 20.3 months, mean wound size 11.6 cm2 at randomization)
Treatment
Topical LL-37 0.5 mg/mL, LL-37 1.6 mg/mL or placebo, in combination with compression therapy
Follow-up
not stated in the source
Study design
Phase 2b double-blind randomized placebo-controlled trial, three arms
Funding
not stated in the source

The post hoc subgroup is hypothesis-generating, not a result.

Read the original source
Venous leg ulcers: 34 participants, healing rate sixfold and threefold at 0.5 and 1.6 mg/mL

Randomized controlled trial

Grönberg A et al. Wound Repair Regen. 2014;22(5):613-21. PMID 25041740.

Healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL (p=0.003 and p=0.088). Mean ulcer area fell 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. The 3.2 mg/mL group did not differ from placebo, so the dose-response is inverted at the top concentration. No local or systemic safety concerns were reported.

Participants / model
34 adults with hard-to-heal venous leg ulcers
Treatment
Topical LL-37 at 0.5, 1.6 or 3.2 mg/mL, or placebo, applied twice weekly
Follow-up
3-week open-label placebo run-in, 4-week randomized double-blind phase, then 4 weeks of follow-up
Study design
Randomized double-blind placebo-controlled first-in-man trial with an open-label run-in
Funding
not stated in the source

The concentrations were applied to an open wound and are not systemic doses.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source
Registry NCT02225366: 4 enrolled, 3 with posted results, 0 serious adverse events

Trial registry record

ClinicalTrials.gov. NCT02225366, phase 1/2 study of intratumoral LL37 in cutaneous or subcutaneous melanoma, with posted results.

NCT02225366, a phase 1/2 study at a single US cancer center, gave weekly intratumoral injections of LL37 into cutaneous or subcutaneous melanoma tumors at least 1 cm in diameter for up to 8 weeks, starting at 250 mcg per tumor with a second cohort at 500 mcg per tumor. Actual enrollment was 4; posted results cover 3 participants (2 in cohort 1, 1 in cohort 2). The study completed on 24 November 2020. Posted safety data report 0 deaths and 0 serious adverse events, with other adverse events in 2 of 2 participants in cohort 1 and in the cohort 2 participant; 1 participant discontinued for lack of efficacy.

Participants / model
4 enrolled patients with melanoma, 3 with posted results
Treatment
Intratumoral LL37 injection, 250 or 500 mcg per tumor weekly
Follow-up
Up to 8 weeks; study completed 24 November 2020
Study design
Phase 1/2 dose-finding study with posted results; outcomes were optimal biological dose by toxicity, antitumor immune response and adverse events
Funding
not stated in the source

The only registered study that injected LL-37 into people. A 3-participant dose-finding record cannot support an efficacy claim in any population.

Read the original source
Searches, 9 October 2026: 2 of 20 registry records gave LL-37 as a drug; no systemic or inhaled human use

PubMed search record

PubMed search run on 9 October 2026: (LL-37 OR ropocamptide) AND (intravenous OR subcutaneous OR intramuscular OR inhaled OR nebulized OR intranasal), humans MeSH term, 40 records. ClinicalTrials.gov intervention-scoped search for LL-37, 20 records, and a PubMed search for LL-37 with KPV, 1 record, run the same day.

A ClinicalTrials.gov intervention-scoped search for LL-37 returned 20 records. Only two gave LL-37 to people as a drug: the topical diabetic foot ulcer cream and the intratumoral melanoma study. The other 18 measured endogenous cathelicidin as a biomarker in saliva, gingival fluid or serum, or tested vitamin D and mouthwashes. A PubMed search for LL-37 or ropocamptide with intravenous, subcutaneous, intramuscular, inhaled, nebulized or intranasal routes, limited to human records, returned 40 records, none of which administered LL-37 systemically or by inhalation to people. A PubMed search for LL-37 with KPV returned 1 record, a 2025 review of host defense peptides in inflammatory bowel disease, not a combination study.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Infection trial: 238 inpatients, genetically modified Lactococcus lactis by mouth, viral RNA clearance 9.80 versus 14.04 days

Randomized controlled trial

Zhao Y et al. J Med Virol. 2023;95(8):e29035. PMID 37605995.

When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo, p<0.01, with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

Participants / model
238 adult inpatients with COVID-19 (Omicron BA.5.1.3 variant)
Treatment
Oral recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium
Follow-up
not stated in the source
Study design
Open-label randomized placebo-controlled single-center study
Funding
not stated in the source

The product is a genetically modified Lactococcus lactis expressing LL-37 given by mouth, not a synthetic LL-37 peptide and not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Read the original source

Studies and sources

PubChem: LL-37 identity and ropocamptide synonym

Chemical identity record

National Library of Medicine. PubChem compound record CID 16198951 (LL-37, human cathelicidin).

LL-37 is the 37-residue C-terminal peptide of human cathelicidin hCAP-18: PubChem CID 16198951, C205H340N60O53, molecular weight 4493, CAS 154947-66-7. Listed synonyms include ropocamptide, which is the INN assigned to the synthetic drug candidate, plus Cap-18 and CAP18.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined 37-residue peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The synthetic peptide, the endogenous peptide measured in saliva and serum, and a live bacterium engineered to express LL-37 are three different things and are kept separate on this page.

Read the original source
Venous leg ulcers: 34 participants, healing rate sixfold and threefold at 0.5 and 1.6 mg/mL

Randomized controlled trial

Grönberg A et al. Wound Repair Regen. 2014;22(5):613-21. PMID 25041740.

Healing rate constants were about sixfold and threefold higher than placebo at 0.5 and 1.6 mg/mL (p=0.003 and p=0.088). Mean ulcer area fell 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. The 3.2 mg/mL group did not differ from placebo, so the dose-response is inverted at the top concentration. No local or systemic safety concerns were reported.

Participants / model
34 adults with hard-to-heal venous leg ulcers
Treatment
Topical LL-37 at 0.5, 1.6 or 3.2 mg/mL, or placebo, applied twice weekly
Follow-up
3-week open-label placebo run-in, 4-week randomized double-blind phase, then 4 weeks of follow-up
Study design
Randomized double-blind placebo-controlled first-in-man trial with an open-label run-in
Funding
not stated in the source

The concentrations were applied to an open wound and are not systemic doses.

Read the original source
HEAL LL-37: 148 patients, phase 2b, no significant healing improvement in the full population

Randomized controlled trial

Mahlapuu M et al. Wound Repair Regen. 2021;29(6):938-950. PMID 34687253.

The efficacy analysis on the full study population did not identify any significant improvement in healing versus placebo. A post hoc analysis found significant improvement in the subgroup with target wounds of at least 10 cm2. The drug was well tolerated and safe at both concentrations.

Participants / model
148 patients with hard-to-heal venous leg ulcers (mean age 67.6 years, median ulcer duration 20.3 months, mean wound size 11.6 cm2 at randomization)
Treatment
Topical LL-37 0.5 mg/mL, LL-37 1.6 mg/mL or placebo, in combination with compression therapy
Follow-up
not stated in the source
Study design
Phase 2b double-blind randomized placebo-controlled trial, three arms
Funding
not stated in the source

The post hoc subgroup is hypothesis-generating, not a result.

Read the original source
Diabetic foot ulcers: LL-37 cream raised granulation index; cytokines and bacterial counts not lowered

Randomized controlled trial

Miranda E et al. Arch Dermatol Res. 2023;315(9):2623-2633. PMID 37480520.

The increase in granulation index was consistently greater with LL-37 at days 7, 14, 21 and 28 (p=0.031, 0.009, 0.006 and 0.037). Wound-fluid IL-1 alpha and TNF-alpha rose in both groups at days 14 and 21 with no significant difference, and the fall in aerobic bacteria colonization was not significantly different between groups. Baseline LL-37 in the ulcers was low in both groups (about 1.07 and 1.11 ng/mg protein).

Participants / model
Patients with diabetic foot ulcer and mild infection; number not stated in the source
Treatment
Topical LL-37 cream or placebo cream, applied twice weekly
Follow-up
4 weeks; study run in Jakarta from January 2020 to June 2021
Study design
Randomized double-blind controlled trial
Funding
not stated in the source

The cream improved a granulation measure and did not lower cytokines or bacterial counts, which is the opposite of the sellers' cytokine-control and antimicrobial-coverage framing.

Read the original source
Registry NCT04098562: phase 2, planned enrollment 40, status unknown, no posted results

Trial registry record

ClinicalTrials.gov. NCT04098562, phase 2 study of LL-37 cream in diabetic foot ulcers.

NCT04098562 is a phase 2 study of LL-37 cream in diabetic foot ulcers with a planned enrollment of 40, a start in October 2019 and completion in January 2020, recorded with an overall status of unknown and no posted results.

Participants / model
Patients with diabetic foot ulcer
Treatment
Topical LL-37 cream, 0.5 mg/mL
Follow-up
Registered October 2019 to January 2020
Study design
Registered healing, bacteriology and inflammation outcomes; no posted results
Funding
not stated in the source

The registration supports that the study existed; the published report supplies the result.

Read the original source
Registry NCT02225366: 4 enrolled, 3 with posted results, 0 serious adverse events

Trial registry record

ClinicalTrials.gov. NCT02225366, phase 1/2 study of intratumoral LL37 in cutaneous or subcutaneous melanoma, with posted results.

NCT02225366, a phase 1/2 study at a single US cancer center, gave weekly intratumoral injections of LL37 into cutaneous or subcutaneous melanoma tumors at least 1 cm in diameter for up to 8 weeks, starting at 250 mcg per tumor with a second cohort at 500 mcg per tumor. Actual enrollment was 4; posted results cover 3 participants (2 in cohort 1, 1 in cohort 2). The study completed on 24 November 2020. Posted safety data report 0 deaths and 0 serious adverse events, with other adverse events in 2 of 2 participants in cohort 1 and in the cohort 2 participant; 1 participant discontinued for lack of efficacy.

Participants / model
4 enrolled patients with melanoma, 3 with posted results
Treatment
Intratumoral LL37 injection, 250 or 500 mcg per tumor weekly
Follow-up
Up to 8 weeks; study completed 24 November 2020
Study design
Phase 1/2 dose-finding study with posted results; outcomes were optimal biological dose by toxicity, antitumor immune response and adverse events
Funding
not stated in the source

The only registered study that injected LL-37 into people. A 3-participant dose-finding record cannot support an efficacy claim in any population.

Read the original source
Infection trial: 238 inpatients, genetically modified Lactococcus lactis by mouth, viral RNA clearance 9.80 versus 14.04 days

Randomized controlled trial

Zhao Y et al. J Med Virol. 2023;95(8):e29035. PMID 37605995.

When started within 6 days of case confirmation, negative conversion time of SARS-CoV-2 RNA was 9.80 days (SD 2.67) versus 14.04 days (SD 5.89) on placebo, p<0.01, with an adjusted hazard ratio for nucleic acid negative outcome of 2.427 (95% CI 1.239 to 4.751, p=0.0097) versus placebo. No severe adverse events were observed during hospitalization and follow-up.

Participants / model
238 adult inpatients with COVID-19 (Omicron BA.5.1.3 variant)
Treatment
Oral recombinant Lactococcus lactis expressing LL-37, a genetically modified bacterium
Follow-up
not stated in the source
Study design
Open-label randomized placebo-controlled single-center study
Funding
not stated in the source

The product is a genetically modified Lactococcus lactis expressing LL-37 given by mouth, not a synthetic LL-37 peptide and not an injection. The endpoint is viral RNA clearance time, not symptoms, hospitalization or death, and the study was open-label at one center.

Read the original source
Test-tube MICs: activity at 100 mM NaCl against some organisms, resistance in others

Cell study

Turner J et al. Antimicrob Agents Chemother. 1998;42(9):2206-14. PMID 9736536.

In radial diffusion and broth microdilution assays, LL-37 showed considerable activity (MIC under 10 micrograms/mL) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci even in media containing 100 mM NaCl. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at 100 mM NaCl but susceptible in low-salt media. Burkholderia cepacia was resistant at either salt concentration. LL-37 bound E. coli lipopolysaccharide with high affinity and permeabilized E. coli membranes.

Participants / model
Bacterial and fungal isolates in vitro
Treatment
LL-37 in radial diffusion and broth microdilution assays
Follow-up
not stated in the source
Study design
In vitro mechanistic study
Funding
not stated in the source

These are test-tube MICs at defined salt concentrations, not evidence that LL-37 clears an infection in a person.

Read the original source
LL-37 with VIP: one test-tube bactericidal assay in four bacterial species

Cell study

Ohta K et al. J Neuroimmunol. 2011;233(1-2):37-45. PMID 21176972.

Bactericidal assays against Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans and Staphylococcus aureus found that the killing effect of vasoactive intestinal peptide or orexin B alone was detectable at low NaCl but attenuated at physiological 150 mM NaCl, and that adding LL-37 restored it. That is an additive in vitro bactericidal observation in four bacterial species.

Participants / model
Bacterial cultures in vitro
Treatment
LL-37 with VIP or orexin B in buffer
Follow-up
not stated in the source
Study design
In vitro bactericidal assays at varying NaCl
Funding
not stated in the source

No human or animal study of the LL-37 and VIP combination was located.

Read the original source
Psoriasis: two-thirds of patients have LL37-specific T cells that track disease activity

Human study

Lande R et al. Nat Commun. 2014;5:5621. PMID 25470744.

Two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4+ and/or CD8+ T cells specific for LL37. Those T cells produce IFN-gamma and, for the CD4+ cells, Th17 cytokines, they can infiltrate lesional skin, and their presence in blood correlates significantly with disease activity.

Participants / model
Patients with moderate-to-severe plaque psoriasis
Treatment
Endogenous and synthetic LL37 used as antigen in T-cell assays
Follow-up
not stated in the source
Study design
Clinical and mechanistic study of T-cell frequency, cytokine production and correlation with disease activity
Funding
not stated in the source

LL37 is a T-cell autoantigen in psoriasis. It is a self-antigen that a substantial fraction of people with this inflammatory skin disease already have T cells against.

Read the original source

Why is LL-37 in C tier?

C fits a plausible mechanism with thin and partly negative outcome data. LL-37 is a real human peptide that has been given to people in four studies, all topical or intratumoral, and the largest trial missed its efficacy analysis in the full population. The sellers' infection, mucosal repair and KPV claims have no human study of the synthetic peptide behind them.