Placental Membrane Products for Foot and Leg Ulcers

(C5CAMP Trial)

Overseen By Bennett Rogers

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: C5 Biomedical

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

Disqualifiers: Pregnancy, Osteomyelitis, End stage renal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

177 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for difficult-to-heal foot and leg ulcers, often seen in individuals with diabetes or vein issues. Researchers aim to determine if human placental membrane products (AM/Single and AM/Double) can improve healing compared to standard care methods. The trial includes several groups, with some receiving standard care and others receiving one or two layers of the placental membrane treatment. It suits those with a diabetic foot ulcer or vein-related leg ulcer that hasn't healed with regular care in the last four weeks. Participants must attend weekly visits and adhere to study requirements. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could enhance healing for those with persistent ulcers.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that products made from the human amniotic membrane, such as AM/Single and AM/Double, hold promise for treating foot and leg ulcers. Research indicates that patients generally tolerate these treatments well. Specifically, studies found that AM/Single led to over 90% complete healing of ulcers without major safety concerns. Similarly, AM/Double has been used safely in clinical settings, with studies noting significant improvement in ulcer healing without serious side effects. Both treatments originate from the human placenta, which has a history of safe use in wound care. These findings suggest that AM/Single and AM/Double are generally safe options for individuals with nonhealing ulcers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AM/Single and AM/Double for foot and leg ulcers because these treatments use human amniotic membrane allografts, which are different from the standard care methods like debridement and moisture management. Amniotic membranes are known for their healing properties, promoting faster tissue regeneration and reducing inflammation. Unlike traditional treatments that focus mainly on managing symptoms, AM/Single and AM/Double could potentially accelerate healing by directly using biological materials that encourage tissue repair. These treatments offer a promising new approach for ulcer healing that could lead to quicker and more effective recovery.

What evidence suggests that this trial's treatments could be effective for foot and leg ulcers?

This trial will compare the effectiveness of different treatments for foot and leg ulcers. Studies have shown that products made from human amniotic membrane (HAM) can significantly speed up the healing of these ulcers. Participants in this trial may receive AM/Single, an air-dried, sterile single-layer human amniotic membrane allograft. Research found that this treatment led to over 90% of ulcers healing completely compared to standard care. Similarly, AM/Double, another treatment option in this trial using two layers, closed diabetic foot ulcers and venous leg ulcers more quickly than standard treatments. These findings suggest that both AM/Single and AM/Double could be promising options for treating these difficult-to-heal wounds. ^{2 3 5 6 7}

Who Is on the Research Team?

Thomas Serena, MD

Principal Investigator

SerenaGroup, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AM/Double
• AM/Single
• Standard of Care

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

Placental membranes, rich in collagen and growth factors, have been developed as a new advanced treatment option for chronic diabetic foot ulcers (DFUs), addressing the limitations of standard care.

While placental products show promise in promoting healing due to their anti-inflammatory and angiogenic properties, more randomized controlled trials are needed to establish their efficacy and optimal application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers. Brantley, JN., Verla, TD.[2019]

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]

Human amniotic membrane (HAM) allograft significantly improves the healing of chronic diabetic foot ulcers (DFUs), with a healing rate 3.88 times higher than standard care alone at 6 weeks and 2.01 times higher at 12 weeks, based on a meta-analysis of 7 studies involving 465 participants.

Patients receiving HAM treatment experienced a shorter time to complete healing by an average of 30.33 days, with no significant increase in adverse events, indicating that HAM is both effective and safe for this condition.

NCBI (Pubmed)

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. Su, YN., Zhao, DY., Li, YH., et al.[2021]

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]

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]

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]

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]

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]

In a pilot study involving 13 patients with chronic varicose leg ulcers that did not respond to standard treatments, the use of amniotic membrane (AM) showed effectiveness in promoting healing and epithelization.

After 2 years, only 23% of the patients experienced a recurrence of their ulcers, suggesting that AM can be a viable treatment option for patients with refractory ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic Membrane in the Treatment of Varicose Ulcers: a Center Experience. Rocha-Neves, J., Ferreria, A., Sousa, J., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9586828/

A Multicenter, Randomized, Controlled, Clinical Trial ... A multicenter, randomized, controlled, clinical trial evaluating dehydrated human amniotic membrane in the treatment of venous leg ulcers.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07078968?aggFilters=status:act,funderType:industry&viewType=Table&rank=3

Study Details | NCT07078968 | A REAL WORLD DATA ... This is a retrospective multi-center study collecting real world evidence on the use of Tri-Membrane Wrap™, Membrane Wrap™, Membrane Wrap-Hydro™ ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hsr2.70819

A Multicenter, Randomized, Controlled, Clinical Trial ... LPM and standard of care, significantly closed more venous leg ulcers and faster than standard of care alone and improved the quality of life ...

4. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=39865

Skin Substitute Grafts/Cellular and Tissue-Based Products ... Use of a dual-layer amniotic membrane in the treatment of diabetic foot ulcers: an observational study. J Wound Care. 2020;29(Sup9):S8-S12. Smiell JM ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06674980

Clinical Trial Assessing Human Placental Membrane ... This study will evaluate the clinical utility of multiple CAMPs in the closure of diabetic foot ulcers and venous leg ulcers in subjects in comparison to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32924804/

Use of a dual-layer amniotic membrane in the treatment ... Background: Despite advances in the treatment, fewer than half of diabetic foot ulcers (DFUs) heal in 12 weeks and 85% of non-traumatic ...

7. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39759&ver=11

Proposed LCD - Skin Substitute Grafts/Cellular and Tissue ... Use of a dual-layer amniotic membrane in the treatment of diabetic foot ulcers: an observational study. Journal of Wound Care. 2020;29(Sup9):S8-S12. Smiell ...