Placental Membrane Products for Foot and Leg Ulcers

(C5CAMP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Thomas Serena, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: C5 Biomedical

Must not be taking: Immunosuppressants, Chemotherapy, Biologics, Hydroxyurea

Disqualifiers: Pregnancy, Osteomyelitis, End stage renal, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the efficacy of multiple human placental membrane products and Standard of Care (SOC) versus SOC alone in the management of nonhealing diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) over 12 weeks using a modified platform trial design.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking immunosuppressants, certain chemotherapy drugs, or hydroxyurea, you may not be eligible to participate.

What data supports the effectiveness of the treatment for foot and leg ulcers?

Research shows that using amniotic membrane (a layer from the placenta) can help heal chronic leg ulcers by promoting tissue growth and reducing inflammation. Studies have demonstrated that it can significantly improve healing in various types of lower limb ulcers, including those that are difficult to treat with standard methods. ^{1 2 3 4 5}

Is the use of placental membrane products for foot and leg ulcers safe?

Research shows that using amniotic membrane (a part of the placenta) for treating foot and leg ulcers is generally safe. Studies found no significant difference in adverse events (unwanted side effects) when compared to standard care, indicating it is a safe option for treating these types of ulcers. ^{1 2 6 7 8}

How is the treatment using placental membrane products for foot and leg ulcers different from other treatments?

Placental membrane products are unique because they use the innermost layer of the placenta, which has special properties like reducing inflammation, fighting bacteria, and promoting healing. These products are more affordable and widely available compared to other skin substitutes, making them a novel option for treating chronic wounds. ^{1 2 3 5 9}

Research Team

Thomas Serena, MD

Principal Investigator

SerenaGroup, Inc.

Eligibility Criteria

This trial is for adults over 18 with type 1 or type 2 diabetes who have nonhealing foot ulcers (DFUs) or venous leg ulcers (VLUs). The ulcer should be between 0.7 cm² and 20.0 cm², present for at least four weeks but not more than a year, and located below the ankle without exposing tendon or bone.

Inclusion Criteria

My tissue oxygen measurement is 40 mmHg or higher.

My TBI score is 0.6 or higher.

My ulcer is between 0.7 and 20.0 cm2 in size after cleaning.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either human placental membrane products and Standard of Care or Standard of Care alone for nonhealing diabetic foot ulcers and venous leg ulcers

12 weeks

Weekly visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AM/Double (Biological)
• AM/Single (Biological)
• Standard of Care (Other)

Trial Overview The study tests if adding human placental membrane products to standard care improves healing of diabetic foot and venous leg ulcers compared to standard care alone. Participants will receive treatments over a period of twelve weeks in this modified platform trial design.

Participant Groups

Group I: AM/Single - VLU Experimental Treatment 1 Intervention

AM/Single is an air-dried, sterile single layer human amniotic membrane allograft.

Group II: AM/Single - DFU Experimental Treatment 1 Intervention

AM/Single is an air-dried, sterile single layer human amniotic membrane allograft.

Group III: AM/Double - VLU Experimental Treatment 1 Intervention

AM/Double is an air-dried, sterile double layer human amniotic membrane allograft.

Group IV: AM/Double - DFU Experimental Treatment 1 Intervention

AM/Double is an air-dried, sterile double layer human amniotic membrane allograft.

Group V: Standard of Care - DFU Active Control 1 Intervention

Debridement, reduction of bacterial burden, and proper moisture balance using dressings. Off-loading using the off-loading boot or total contact cast (TCC).

Group VI: Standard of Care - VLU Active Control 1 Intervention

Debridement, reduction of bacterial burden, and proper moisture balance using dressings. Compression using multilayer compression wraps.

Who Is Running the Clinical Trial?

C5 Biomedical

Lead Sponsor

Trials

1

Recruited

180+

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Findings from Research

In a pilot study involving 15 patients with chronic venous leg ulcers, amniotic membrane (AM) grafts demonstrated a 100% engraftment rate and significantly improved healing, with granulation tissue increasing from 17% to 69% over 14 days.

AM transplantation was found to be safe, with no adverse events reported, and resulted in a significant reduction in ulcer-related pain, making it a promising low-cost alternative for treating chronic leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of amniotic membrane transplantation in the treatment of venous leg ulcers. Mermet, I., Pottier, N., Sainthillier, JM., et al.[2022]

Amniotic membrane transplantation showed promising results in treating refractory chronic leg ulcers, with complete re-epithelialization achieved in one case by week 8 and an average wound size reduction of 81.93% by week 16 across four ulcers.

The treatment also significantly reduced pain intensity by 86.6% without any observed adverse effects, suggesting it is a safe and effective alternative for patients with difficult-to-treat ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in the treatment of chronic lower limb ulcers. Alsina-Gibert, M., Pedregosa-Fauste, S.[2012]

A fresh human placental membrane allograft was successfully used to heal a chronic venous ulcer in an 89-year-old woman, demonstrating its potential effectiveness in treating long-standing wounds.

After 60 days of treatment, the ulcer was completely healed, indicating that the amniochorionic membrane can be a viable therapeutic option for chronic vascular ulcers that do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healing of a chronic ulcer of the lower limb of venous origin with fresh human amniochorionic membrane allograft Piamo, A., García, M., Romero, D., et al.[2023]

Fetal membranes, specifically amnion and chorion, can be effectively used as biological dressings for treating various types of lower extremity ulcers, as demonstrated through multiple case histories.

The authors advocate for the broader adoption of fetal membranes in clinical practice, highlighting their potential benefits in enhancing healing for pedal ulcerations encountered by podiatrists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications for the use of amnion and chorion in podiatric medicine and surgery. Boc, SF., Chairman, EL., Freed, EL.[2009]

In a randomized controlled trial involving 60 patients with chronic venous leg ulcers, the use of dehydrated human amnion and chorion allograft (dHACA) combined with standard care resulted in a significantly higher healing rate (75%) compared to standard care alone (30%) after 12 weeks.

The treatment was found to be safe, with a 63.5% adverse event rate, but none of the adverse events were related to the graft or procedure, indicating that dHACA is a beneficial and safe option for treating chronic venous leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers. Serena, TE., Orgill, DP., Armstrong, DG., et al.[2023]

The use of human amnion/chorion membrane in conjunction with standard therapy significantly improves healing rates for diabetic foot ulcers (DFUs), with a marked reduction in incomplete healing wounds compared to standard care alone, as shown in a meta-analysis of seven randomized controlled trials involving 352 initial studies.

Optimal assessment times for evaluating wound healing progress with amnion treatment are at 4 weeks and 12 weeks, indicating that early and later evaluations are crucial for understanding treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Time Sensitivity of Amniotic Membrane treatment in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-analysis. Laurent, I., Astère, M., Wang, KR., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of amniotic membrane transplantation in the treatment of venous leg ulcers. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in the treatment of chronic lower limb ulcers. [2012]

3. Colombia pubmed.ncbi.nlm.nih.gov

Healing of a chronic ulcer of the lower limb of venous origin with fresh human amniochorionic membrane allograft [2023]

4. Portugal pubmed.ncbi.nlm.nih.gov

Amniotic Membrane in the Treatment of Varicose Ulcers: a Center Experience. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Implications for the use of amnion and chorion in podiatric medicine and surgery. [2009]

6. United States pubmed.ncbi.nlm.nih.gov

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Human amniotic membrane allograft, a novel treatment for chronic diabetic foot ulcers: A systematic review and meta-analysis of randomised controlled trials. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Time Sensitivity of Amniotic Membrane treatment in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-analysis. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers. [2019]