Amnio Products for Diabetic Foot Ulcers and Venous Leg Ulcers

Not yet recruiting at 2 trial locations

Overseen By Thomas Serena, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stability Biologics

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

Disqualifiers: Life expectancy < 6 months, Infection, Osteomyelitis, HbA1c ≥ 12%, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different amniotic membrane products in treating stubborn diabetic foot and venous leg ulcers compared to standard treatments. Participants will receive either one of several cellular and matrix-like products (such as AmnioCore, AmnioCore Pro, or Amnio Quad-Core) or follow a standard care routine to determine which option promotes better ulcer healing. Ideal participants include those with diabetes who have had a persistent foot ulcer for at least four weeks, impacting their daily activities. As an unphased trial, this study provides participants the chance to contribute to innovative research that could enhance treatment options for chronic ulcers.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking immunosuppressants, cytotoxic chemotherapy, medications that interfere with wound healing, or hydroxyurea.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking immunosuppressants, certain chemotherapy drugs, or hydroxyurea, as these may interfere with wound healing.

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

Research shows that using amniotic membrane allografts, which are tissue grafts, to treat foot and leg ulcers is generally safe and well-tolerated. Studies on products like AmnioCore, AmnioCore Pro, AmnioCore Pro +, Amnio Quad-Core, and Amnio Tri-Core have demonstrated positive safety results.

For diabetic foot ulcers (DFUs), these human tissue grafts are considered effective and safe. Some studies have shown that they help heal chronic DFUs without major side effects and outperform standard care alone.

For venous leg ulcers (VLUs), the evidence is less clear, but products like AmnioCore Pro and Amnio Tri-Core are used similarly, suggesting they are also safe.

Overall, these treatments rely on well-researched materials and have a good safety record for treating ulcers. However, individual experiences may vary, and participating in a clinical trial will include careful monitoring of safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these amniotic membrane allograft treatments for foot and leg ulcers because they offer a novel approach that could enhance healing. Unlike standard care, which usually involves debridement, moisture balance, and off-loading techniques, these treatments use layers of amniotic tissue to potentially speed up recovery and improve outcomes. AmnioCore - DFU, AmnioCore Pro, and Amnio Quad-Core - DFU focus on diabetic foot ulcers, with varying layers of amniotic tissue that might provide extra protection and promote tissue regeneration. Amnio Tri-Core - VLU and AmnioCore Pro - VLU are designed for venous leg ulcers, using advanced three-layer structures to improve healing. This innovative use of natural, regenerative tissue is what sets these treatments apart and has researchers eager to see the results.

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

This trial will evaluate various amniotic membrane products for foot and leg ulcers. Studies have shown that products like AmnioCore, which participants in this trial may receive, effectively heal diabetic foot ulcers. For example, one study found that 94.4% of wounds treated with these membranes stayed closed after 9–12 months. Another study demonstrated that these membranes help diabetic ulcers heal quickly. In this trial, AmnioCore Pro is another treatment option being tested, and research suggests it may aid in healing venous leg ulcers. Additionally, Amnio Quad-Core, also under study in this trial, has proven effective in treating diabetic foot ulcers when used with standard care. These treatments utilize the natural healing properties of amniotic membranes to help wounds close. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with nonhealing diabetic foot or venous leg ulcers that are larger than a dime but smaller than a bottle cap, present for at least one month but not more than a year. It's not suitable for those with infected ulcers or ulcers exposing tendon or bone.

Inclusion Criteria

Is your foot or leg ulcer between 1-20 cm2?

Has your foot or leg ulcer been present for at least a month but no longer than a year?

Exclusion Criteria

Does your foot ulcer expose tendon or bone?

Is your foot or leg ulcer infected or has it been infected recently?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple CAMPs plus SOC or SOC alone for the management of nonhealing diabetic foot and venous leg ulcers

12 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AmnioCore - DFU
• AmnioCore Pro
• AmnioCore Pro +
• Amnio Quad-Core - DFU
• Amnio Tri-Core - VLU
• Standard of Care-DFU
• Standard of Care-VLU

Trial Overview The study compares various treatments including cellular and matrix-like products (CAMPs) combined with standard care versus standard care alone in healing diabetic foot and venous leg ulcers across multiple centers.

How Is the Trial Designed?

Group I: Amniocore Pro + - DFU Experimental Treatment 1 Intervention

Dual layer, amnion/chorion membrane allograft.

Group II: AmnioCore Pro - VLU Experimental Treatment 1 Intervention

Three layer, amnion/chorion/amnion membrane allograft.

Group III: AmnioCore - DFU Experimental Treatment 1 Intervention

Dual layer, amniotic membrane allograft.

Group IV: Amnio Tri-Core - VLU Experimental Treatment 1 Intervention

Three layer, amniotic membrane allograft.

Group V: Amnio Quad-Core - DFU Experimental Treatment 1 Intervention

Four layer, amniotic membrane allograft.

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

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

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

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

AmnioCore - DFU is already approved in United States for the following indications:

Approved in United States as AmnioCore for:

• Diabetic Foot Ulcers (DFUs)
• Venous Leg Ulcers (VLUs)

Who Is Running the Clinical Trial?

Stability Biologics

Lead Sponsor

Trials

1

Recruited

320+

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Published Research Related to This Trial

The study found that the combination of hydrogen peroxide (H2O2) with the monomers TEGDMA and UDMA significantly increased their toxicity to human gingival fibroblasts (HGF) and human pulpal fibroblasts (HPF), indicating a potential risk when these substances are used together in dental applications.

In contrast, the monomers HEMA and BisGMA did not show increased toxicity when combined with H2O2, suggesting that they may be safer options in terms of cellular viability in the presence of oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity potentiation by H2O2 with components of dental restorative materials on human oral cells. Reichl, FX., Seiss, M., Marquardt, W., et al.[2013]

In a study involving 29 adults with diabetes and chronic foot ulcers, the use of dehydrated amniotic membrane allograft (DAMA) combined with standard care led to a significant increase in complete wound closure rates, with 35% achieving closure compared to 0% in the standard care group within 6 weeks.

No treatment-related adverse events were reported, indicating that DAMA is a safe option for managing diabetic foot ulcers, although further research is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Randomized, Multicenter, Controlled Evaluation of the Use of Dehydrated Amniotic Membrane Allograft Compared to Standard of Care for the Closure of Chronic Diabetic Foot Ulcer. Snyder, RJ., Shimozaki, K., Tallis, A., et al.[2017]

In a randomized controlled trial involving 60 subjects with nonhealing diabetic foot ulcers, dehydrated human amnion and chorion allograft (dHACA) demonstrated a significantly faster healing time compared to the tissue-engineered skin substitute (TESS), with mean healing times of 32 days for dHACA versus 63 days for TESS at 12 weeks.

The dHACA group also showed a higher healing rate of 90% compared to 40% for the TESS group, and it was more cost-effective, with an average cost of $2,200 for dHACA compared to $7,900 for TESS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental Membrane Provides Improved Healing Efficacy and Lower Cost Versus a Tissue-Engineered Human Skin in the Treatment of Diabetic Foot Ulcerations. Glat, P., Orgill, DP., Galiano, R., et al.[2022]

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]

The human acellular amniotic membrane (HAAM) was found to be effective in treating venous lower limb ulcers, with complete healing in 2 out of 4 patients and significant reductions in ulcer size and depth in all cases.

HAAM treatment not only led to improved healing outcomes, such as >50% granulation tissue formation and the disappearance of infection signs, but it also proved to be more cost-effective compared to traditional treatments like skin autografts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human acellular amniotic membrane is adopted to treat venous ulcers. Wu, Z., Liu, X., Yuan, D., et al.[2020]

In a study of 26 patients with diabetic foot ulcers (DFUs) that had not healed significantly after standard care, 65% achieved complete closure within 12 weeks when treated with a dual-layer amniotic membrane (DLAM).

The results suggest that DLAM may be particularly effective for larger, more resistant ulcers, indicating its potential as a promising treatment option alongside standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a dual-layer amniotic membrane in the treatment of diabetic foot ulcers: an observational study. Sledge, I., Maislin, D., Bernarducci, D., et al.[2022]

In a study using the Guinea Pig Maximization Test, tri-ethylene glycol mono-methacrylate (TEGMA) was found to have a lower risk of causing allergic skin reactions compared to 2-hydroxy ethyl methacrylate (2-HEMA).

TEGMA's adverse effects were similar to those of highly purified glyceryl mono-methacrylate (GM), suggesting it could be a safer alternative for use in primers in dermatological applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guinea Pig Maximization Test of tri-ethylene glycol mono-methacrylate. Akiyama, T., Manabe, A., Tani, C., et al.[2019]

In a study of 21 patients undergoing lower extremity surgery, the use of dehydrated human amnion and chorion allograft (dHACA) significantly improved post-treatment AOFAS scores from 35.8 to 87.5, indicating enhanced overall function and reduced pain.

The application of dHACA was associated with fewer wound complications, including no instances of wound dehiscence, suggesting it may be a beneficial adjunct in foot and ankle surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wound repair, safety, and functional outcomes in reconstructive lower extremity foot and ankle surgery using a dehydrated amnion/chorion allograft membrane. Tacktill, JZ., Rasor, Z., Adams, J., et al.[2022]

In a study of eight patients with diabetic foot ulcers (DFUs) that did not heal with standard care, the addition of dehydrated amniotic membrane allograft (DAMA) led to complete wound closure in an average of 9.2 weeks.

Patients who received three applications of DAMA experienced faster healing times compared to those who received only one application, indicating that multiple treatments may enhance the efficacy of DAMA in promoting wound closure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Case Series of a Dehydrated Amniotic Membrane Allograft for Treatment of Unresolved Diabetic Foot Ulcers. Rosenblum, BI.[2017]

Duraflur varnish demonstrated better biocompatibility compared to AH-26, as it resulted in higher cell viability of human gingival fibroblasts at various dilutions, particularly at lower concentrations.

While Duraflur showed comparable cell viability to AH-Plus at the 1/8 dilution, further testing is necessary to fully assess its safety and biocompatibility in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity of two resin-based sealers and a fluoride varnish on human gingival fibroblasts. Parirokh, M., Forghani, FR., Paseban, H., et al.[2022]

The study identified a total of 32 organic compounds leached from four different dental filling materials, highlighting the potential for harmful substances to impact biocompatibility.

Common components like HEMA, HC, and CQ were found in all tested materials, suggesting that the allergenic potential and overall safety may vary significantly between different dental composites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of organic eluates from four polymer-based dental filling materials. Michelsen, VB., Lygre, H., Skålevik, R., et al.[2019]

The study assessed the cytotoxicity of common dental resin monomers on human gingival fibroblasts (HGFs) using the xCELLigence system, revealing that UDMA and BisGMA had the highest toxicity with EC(50) values of 0.20 and 0.08 mmol/L, respectively.

The xCELLigence system proved to be an effective tool for real-time monitoring of cell viability, suggesting its potential for rapid toxicity testing of various substances in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Urcan, E., Haertel, U., Styllou, M., et al.[2022]

Citations

1. journals.sagepub.com journals.sagepub.com/doi/full/10.1177/15347346241276697

Randomized Controlled Trial to Compare AmnioExcel ... Our objective was to compare clinical outcomes in diabetic foot ulcers (DFU) treated with AmnioExcel ® applied weekly (AMX1) or biweekly (AMX2) over a 12-week ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7949407/

Human amniotic membrane allograft, a novel treatment for ... Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs. Keywords: diabetic foot ...

3. journals.lww.com journals.lww.com/prsgo/fulltext/2023/10000/a_prospective_multicenter_study_of_a_weekly.7.aspx

A Prospective Multicenter Study of a Weekly Application... This study was a prospective trial of twenty patients with nonhealing diabetic foot wounds receiving weekly application of viable human amniotic membrane ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9472416/

Human amniotic membrane products for patients with ... Many studies have shown that DHACA as a treatment for diabetic foot ulcers is more effective than standard wound care alone. For further ...

5. jfootankleres.biomedcentral.com jfootankleres.biomedcentral.com/articles/10.1186/s13047-022-00575-y

Human amniotic membrane products for patients with diabetic ... The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial.

6. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39864&ver=2

Skin Substitute Grafts/Cellular and Tissue-Based Products ... This LCD covers skin substitute grafts/cellular and tissue-based products (CTP) for the treatment of diabetic foot ulcers (DFU) and venous leg ulcers (VLU) in ...

7. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/skin-soft-tissue-substitutes.pdf

Skin and Soft Tissue Substitutes Human amniotic membrane allograft, a novel treatment for chronic diabetic foot ulcers: A systematic review and meta-analysis of randomized ...

8. withpower.com withpower.com/trial/amnio-products-for-foot-and-leg-ulcers-2ae59

Amnio Products for Foot and Leg Ulcers · Info for Participants Research shows that using dehydrated amniotic membrane allografts, like those in AmnioCore, can help heal diabetic foot ulcers more effectively than standard ...