Amniotic Tissue Treatments for Diabetic Foot Ulcers

Recruiting at 8 trial locations

Overseen By Frank Burrows III, MBA, EMT, BCMAS, CWCA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Tides Medical

Must not be taking: Immune-suppressants, Chemotherapy, Topical steroids, others

Disqualifiers: Cancer, HIV, Hepatitis C, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to treat diabetic foot ulcers using various amniotic tissue grafts (a type of biological bandage made from placental tissue) alongside standard care. The goal is to determine if these grafts enhance healing compared to standard treatments alone. Individuals with a diabetic foot ulcer lasting more than four weeks but less than a year, who have not experienced significant healing, might be suitable candidates for this study. As an unphased trial, it provides patients the chance to contribute to innovative research that could enhance future treatment options.

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 have been on immune-suppressants, certain chemotherapy drugs, or topical steroids on the ulcer within a month before the study. If you are on any investigational drugs or products, you must stop them at least 30 days before the study.

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

Research has shown that treatments using amniotic tissue, like those in this trial, have been studied for safety in treating various conditions. Previous studies found that these treatments are usually well-tolerated by patients. For instance, individuals using amniotic tissue for wound care reported few serious side effects. Most side effects, if they occurred, were mild and temporary, such as minor skin irritation at the application site.

Amniotic tissue is also used in other medical areas, and past use suggests it is safe. It comes from the placenta, a natural and safe source for these treatments. This trial tests different types of amniotic tissue layers to help heal wounds, such as diabetic foot ulcers.

While this trial doesn't have specific results yet, the treatments being tested resemble those already studied, which have shown few adverse effects. This offers some reassurance about their safety for participants.

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of amniotic tissue treatments for diabetic foot ulcers because these treatments harness the natural healing properties of the placenta. Unlike standard care options, which typically involve dressings and offloading, the amniotic membrane allografts provide a natural scaffold that supports cellular attachment and infiltration, enhancing the body's wound healing processes. These allografts are composed of multiple layers, including epithelial cells and a stromal matrix, which not only protect the wound but also store growth factors that can accelerate healing. By leveraging these unique biological materials, amniotic tissue treatments have the potential to improve healing outcomes for patients with chronic diabetic foot ulcers.

What evidence suggests that this trial's amniotic tissue treatments could be effective for diabetic foot ulcers?

This trial will compare different configurations of amniotic tissue treatments for diabetic foot ulcers. Studies have shown that treatments using amniotic tissue effectively heal these ulcers. Specifically, dehydrated human amnion/chorion membrane (dHACM) allografts help wounds heal quickly, with 94.4% remaining closed after 9 to 12 months. Research indicates that these treatments promote faster healing with fewer complications. The amniotic membrane acts as a natural support, aiding the body's healing by allowing cells to attach and grow. Overall, evidence suggests that amniotic tissue treatments have strong potential to heal chronic diabetic foot ulcers. ^{1 2 3 4 5}

Who Is on the Research Team?

David G Armstrong, DPM, MD, PhD

Principal Investigator

Keck School of Medicine of USC

Frank Burrows, MBA, EMT, BCMAS, CWCA

Principal Investigator

Tides Medical

Are You a Good Fit for This Trial?

This trial is for individuals with chronic non-healing diabetic foot ulcers. Participants should have a history of diabetes and an open wound on the foot that hasn't healed over time despite standard care.

Inclusion Criteria

My ulcer has not been under pressure for at least 14 days.

My ulcer is between 1.0 and 25 cm2 in size.

I am willing to use birth control and take pregnancy tests if I can become pregnant.

Exclusion Criteria

My ulcer has not been treated with any therapies that are not allowed.

I have been diagnosed with HIV or Hepatitis C.

My ulcer is not caused by diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Amnion/Chorion/Amnion allograft, Amnion/Chorion allograft, and/or Amnion/Amnion allograft, plus Standard of Care for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amniotic Tissue(s)

Trial Overview

The study is testing the safety and effectiveness of different types of amniotic tissue treatments (Amnion/Chorion/Amnion, Amnion/Chorion, or Amnion/Amnion allografts) plus standard care versus just standard care alone in healing diabetic foot ulcers after 12 weeks.

How Is the Trial Designed?

Group I: "Amnion/Chorion/Amnion" common/general allograft configuration Experimental Treatment 1 Intervention

Topical application of placental allograft on to surface of open chronic diabetic foot ulcer using a tri-layer dehydrated amniotic membrane allograft for the treatment of DFUs. Human amniotic membrane is a thin collagenous membrane derived from the submucosa of the placenta, the organ that connects the developing fetus to the mother's uterus. A human amniotic membrane consists of multiple layers including epithelial cells, a basement membrane, and a stromal matrix which provides a natural scaffold that allows cellular attachment or infiltration and growth factor storage.

Group II: "Amnion/Chorion" common/general allograft configuration Experimental Treatment 1 Intervention

Topical application of placental allograft on to surface of open chronic diabetic foot ulcer using a dehydrated human amniotic membrane allograft comprised of a tri-layer membrane (amnion/intermediate layer/chorion) which provides a natural scaffold that allows cellular attachment and infiltration. Human amniotic membrane is a thin collagenous membrane derived from the submucosa of the placenta. A human amniotic membrane consists of multiple layers including epithelial cells, a basement membrane, and a stromal matrix. Graft provides a protective cover and supports the body's wound healing processes. This allograft is supplied sterile and not intended to be removed.

Group III: "Amnion/Amnion" common/general allograft configuration Experimental Treatment 1 Intervention

Topical application of placental allograft on to surface of open chronic diabetic foot ulcer using a dual layer dehydrated human amniotic membrane allograft. Human amniotic membrane is a thin collagenous membrane derived from the submucosa of the placenta, the organ that connects the developing fetus to the mother's uterus. A human amniotic membrane consists of multiple layers including epithelial cells, a basement membrane, and a stromal matrix which provides a natural scaffold that allows cellular attachment or infiltration and growth factor storage. This allograft provides a protective cover and supports the body's wound healing process. This allograft is supplied sterile and not intended to be removed.

Group IV: Standard of Care Active Control 1 Intervention

Standard of Care (SOC) for open chronic diabetic foot ulcer using a calcium alginate dressing and will have a silicone non-adherent dressing (MepitelTM or equivalent), a padded 3-layer dressing comprised of 4x4 gauze pads, soft roll, compressive wrap and Coban (Threeflex 3-layer or equivalent) applied. Offloading of the DFU (removable offloading boot or total contact casting \[TCC\] if the subject's foot is too large for a removable offloading boot), appropriate sharp or surgical debridement, and infection management. Graft provides a protective cover and supports the body's wound healing processes. This allograft is supplied sterile and not intended to be removed.

Amniotic Tissue(s) is already approved in United States for the following indications:

Approved in United States as Dehydrated Amniotic Membrane Allograft for:

• Chronic non-healing diabetic foot ulcers

Who Is Running the Clinical Trial?

Tides Medical

Lead Sponsor

Trials

3

Recruited

500+

Professional Education and Research Institute

Collaborator

Trials

16

Recruited

1,400+

Published Research Related to This Trial

In a case series of five patients with chronic non-healing wounds, the use of dehydrated human amnion/chorion membrane allograft resulted in a significant mean area reduction of 43% at 3 weeks, with complete healing achieved in a median time of 64 days.

The treatment was safe, with no adverse events reported, and was easy to administer, indicating that dehydrated amnion/chorion membrane allograft could be an effective option for patients whose wounds have not responded to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane is a potential regenerative option for chronic non-healing wounds: a report of five cases receiving dehydrated human amnion/chorion membrane allograft. Mrugala, A., Sui, A., Plummer, M., et al.[2021]

In a study comparing dehydrated human amnion and chorion allograft (dHACA) to standard care for chronic diabetic foot ulcers, 70% of wounds treated with dHACA healed at 6 weeks, compared to only 15% with standard care.

At 12 weeks, dHACA treatment resulted in 85% healing of wounds, significantly faster than the 25% healing rate in the standard care group, demonstrating its efficacy in promoting wound closure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial. DiDomenico, LA., Orgill, DP., Galiano, RD., et al.[2022]

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]

Human amnion chorion membrane allografts (HACMAs) significantly reduce healing time and increase the percentage of complete healing in chronic diabetic foot ulcers (DFUs) compared to standard treatments, based on a review of 24 studies published between 2016 and 2020.

HACMAs are not only effective but also more cost-efficient and less wasteful than other wound care products, making them a practical option for treating complex DFUs, including those with exposed tendon or bone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Amnion Chorion Membrane Allografts in the Treatment of Chronic Diabetic Foot Ulcers: A Literature Review. Oropallo, A., Goodwin, A., Morrissey, M., et al.[2023]

In a study using a rat model, both dehydrated amnion/chorion grafts (dHACM) and hypothermically stored amniotic membrane grafts (HSAM) significantly improved wound healing compared to untreated wounds, indicating their potential effectiveness in treating chronic wounds.

HSAM grafts were found to promote better tissue regeneration than dHACM meshed grafts, as evidenced by superior collagen matrix formation and the development of hair follicles and glands, highlighting the importance of processing methods in enhancing wound healing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Skin Regeneration Using a Novel Amniotic-derived Tissue Graft. Mowry, KC., Bonvallet, PP., Bellis, SL.[2018]

Amnion and amniotic tissue have been effectively used for over 100 years to treat both acute and chronic wounds, with recent studies highlighting their benefits for full-thickness diabetic wounds in the lower extremities.

Current research indicates that amnion products can significantly enhance healing potential, reduce healing times, and lower instances of pain, drainage, and infection in treated wounds, although further studies are needed to compare the various amnion products available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amnion: The Ideal Scaffold for Treating Full-Thickness Wounds of the Lower Extremity. McKenna, B., Summers, NJ.[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]

In a study of 63 patients with diabetes and chronic foot ulcers, 40% of the ulcers closed after 12 weeks of treatment with a chorioamniotic allograft, with smaller ulcers showing better closure rates (57% for small ulcers compared to 10% for large ulcers).

The treatment was found to be safe, with no unexpected adverse events reported, supporting its use as a wound cover for chronic foot ulcers in patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human placental membrane as a wound cover for chronic diabetic foot ulcers: a prospective, postmarket, CLOSURE study. Pacaccio, DJ., Cazzell, SM., Halperin, GJ., et al.[2019]

The study focuses on diabetic patients with neuropathic foot ulcers, which are difficult to heal and can lead to severe complications like infections and amputations.

The new amniotic membrane-based allograft shows promise as a treatment option, potentially improving healing outcomes compared to traditional conservative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using amniotic membrane allografts in the treatment of neuropathic foot ulcers. Shah, AP.[2016]

Citations

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sciencedirect.com

sciencedirect.com/science/article/pii/S2213909513000402

Dehydrated human amnion/chorion membrane allografts in ...

Treatment with dHACM allografts promotes rapid healing of diabetic ulcers. 94.4% of wounds healed with dHACM remained closed after 9–12 months.

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pmc.ncbi.nlm.nih.gov/articles/PMC5630554/

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Diabetic foot ulcers (DFUs) are complex chronic wounds which have a major long-term impact on the morbidity, mortality and quality of patients.

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

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A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers ...

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tandfonline.com/doi/full/10.1080/14712598.2020.1787979

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Amniofix and other dHACM (dehydrated human amniotic/chorionic membrane) therapies reported faster and complete healing with lower complication rates, when ...

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cureus.com

cureus.com/articles/193767-assessing-the-application-and-effectiveness-of-human-amniotic-membrane-in-the-management-of-venous-and-diabetic-ulcers-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials

A Systematic Review and Meta-Analysis of Randomized ...

This study aimed to assess the efficacy of human amniotic membranes (HAM) in treating venous and diabetic ulcers, which often pose ...