Placental-Based Treatment for Diabetic Foot Ulcers

Overseen By Thomas Serena

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Applied Biologics, LLC

Must not be taking: Immunosuppressants, Chemotherapy, Steroids

Disqualifiers: Infection, Osteomyelitis, Charcot foot, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SLAM, which uses a special layer from the placenta to aid in healing diabetic foot ulcers. Researchers aim to determine if adding SLAM to the usual care—cleaning and protecting the ulcer—enhances healing compared to usual care alone. It suits individuals with diabetes who have foot ulcers unhealed after at least four weeks of standard treatment. The ulcer must be on the foot and meet specific size and location criteria. Participants must attend weekly study visits and use prescribed footwear to aid healing. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could improve future treatments for diabetic foot 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 on immunosuppressants or high doses of corticosteroids, you may not be eligible to participate.

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

Research has shown that a single layer of amniotic membrane (SLAM) can aid in healing stubborn diabetic foot sores. Studies have found that amniotic membrane treatments, such as SLAM, accelerate healing compared to traditional methods and are generally well-tolerated.

One study specifically examined SLAM for diabetic foot sores and found no major safety issues, indicating its safety for similar conditions.

Overall, research supports SLAM as a safe and effective option for treating diabetic foot sores, with evidence demonstrating its healing benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for diabetic foot ulcers, which involves cleaning, debridement, moisture balance, and offloading, the new treatment option, SLAM, offers a unique approach. SLAM uses a single layer amniotic membrane, which is derived from the placenta. This membrane is thought to promote healing by providing a natural barrier and delivering growth factors that enhance tissue regeneration. Researchers are excited about this treatment because it has the potential to speed up healing and improve outcomes for patients with diabetic foot ulcers, offering a promising alternative to the traditional methods.

What evidence suggests that SLAM might be an effective treatment for diabetic foot ulcers?

This trial will compare the effectiveness of a single-layer amniotic membrane (SLAM) combined with standard of care (SOC) to SOC alone for treating diabetic foot ulcers. Studies have shown that SLAM can significantly speed up healing in diabetic foot ulcers that are not healing well. In one study, over 90% of ulcers treated with SLAM completely healed, outperforming standard care alone. Another review found strong evidence that amniotic membranes help heal diabetic ulcers. This treatment provides a natural barrier that supports the skin's healing process. Additionally, most ulcers treated with similar amniotic membrane products remained closed for 9–12 months, demonstrating long-lasting effectiveness. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with type 1 or 2 diabetes who have a foot ulcer that's been there between 4 weeks to a year, measuring 0.7-20 cm² post-debridement. The ulcer should be on the foot below the ankle and not expose tendon or bone. Participants need adequate blood flow as shown by specific tests (ABI, TBI, TCOM, PVR).

Inclusion Criteria

I have been diagnosed with type 1 or type 2 diabetes.

My ulcer is between 0.7 and 20.0 cm2 after cleaning.

My ulcer has been present for 1 to 12 months before my first screening visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single layer amniotic membrane (SLAM) and standard of care (SOC) or SOC alone for the management of nonhealing diabetic foot ulcers

12 weeks

Weekly visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SLAM

Trial Overview The study compares two approaches: one group receives a placental-based allograft plus standard wound care (SLAM + SOC), while the other gets just standard wound care (SOC). It aims to see if adding the allograft improves healing in nonhealing diabetic foot ulcers.

How Is the Trial Designed?

Group I: SLAM + SOC Experimental Treatment 1 Intervention

Single layer amniotic membrane (SLAM) + SOC

Group II: Standard of Care Active Control 1 Intervention

Other: Standard of Care Standard of care will be cleaning, debridement, ulcer moisture balance, and offloading.

Who Is Running the Clinical Trial?

Applied Biologics, LLC

Lead Sponsor

Trials

3

Recruited

700+

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Published Research Related to This Trial

In a study involving 21 men with chronic venous leg ulcers (VLUs) that had not healed after at least 12 weeks of standard therapy, the application of a human viable wound matrix (hVWM) from cryopreserved placental tissue led to complete healing in 53% of cases.

The use of hVWM resulted in a significant average reduction in ulcer size of 79% over approximately 11 weeks, with a healing rate of 1.69% per day, compared to only 0.73% per day with standard therapy, demonstrating its superior efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of cryopreserved placental tissue wound matrix in the management of chronic venous leg ulcers. Farivar, BS., Toursavadkohi, S., Monahan, TS., et al.[2020]

Subcutaneous application of human placental mesenchymal stem cells (PMSCs) significantly accelerates wound healing in diabetic foot ulcers, as demonstrated in an in vivo study with Goto-Kakizaki rats.

PMSCs modulate the immune response by regulating inflammation through the secretion of pro- and anti-inflammatory factors, with interleukin-10 (IL-10) playing a key role in this process, suggesting a potential therapeutic mechanism for treating diabetic dermal wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation. Wang, H., Chen, L., Liu, Y., et al.[2022]

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 of 7,869 Medicare patients with diabetic foot ulcers, those treated with viable cryopreserved placental membrane (vCPM) experienced significantly lower rates of ulcer recurrence at 30, 90, 180, and 365 days compared to other cellular and acellular tissue-based products, with reductions up to 58.5% at one year.

Patients receiving vCPM also had a 2.3 percentage point reduction in one-year mortality compared to those treated with other cellular and acellular products, highlighting the potential of vCPM as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreserved Placental Membrane Allograft Reduces the Likelihood of Developing a New or Recurring Foot Ulcer and All-Cause Mortality in Diabetic Patients When Compared with Other Cellular- and Tissue-Based Products. DaVanzo, J., Hartzman, A., Surfield, C., et al.[2023]

In a study involving 20 patients with nonhealing diabetic foot ulcers, 85% of those treated with cryopreserved viable human amnion membrane allograft (vHAMA) in addition to standard care healed within 12 weeks, demonstrating its efficacy.

The treatment led to significant healing, with 50% of wounds healing by 6 weeks and an average healing time of 46.6 days, indicating that vHAMA is a promising option for patients who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Multicenter Study of a Weekly Application Regimen of Viable Human Amnion Membrane Allograft in the Management of Nonhealing Diabetic Foot Ulcers. Galiano, RD., Orgill, DP., Armstrong, DG., et al.[2023]

In a study involving 100 patients with non-healing wounds, those treated with topical placental extract showed significantly better healing outcomes, with 67.5% achieving over 50% epithelialisation compared to only 23.3% in the control group.

The study suggests that placental extract can be an effective topical treatment for chronic wounds, highlighting its potential role in enhancing wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial to determine the role of placental extract in the treatment of chronic non-healing wounds. Shukla, VK., Rasheed, MA., Kumar, M., et al.[2004]

The study demonstrated that using human placenta-derived mesenchymal stem cells (hPDMSCs) in nanofibrous scaffolds significantly accelerated healing in diabetic foot ulcers (DFUs), with a 66% reduction in wound size for the hPDMSCs group and 71% for the hPDMSCs plus platelet-rich plasma (PRP) group over 12 weeks.

Both treatment groups (hPDMSCs and hPDMSCs with PRP) showed significant improvements in wound closure and pain-free walking distance compared to the control group, indicating that hPDMSCs can enhance healing and promote new capillary formation in DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial. Meamar, R., Ghasemi-Mobarakeh, L., Norouzi, MR., 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]

Cenplacel (PDA-002), derived from human placenta, was found to be safe and well tolerated in a phase 1 study involving 15 patients with peripheral arterial disease and diabetic foot ulcers, with no serious adverse events reported.

Preliminary results showed that cenplacel treatment led to ulcer healing in seven patients (five complete and two partial) within three months, and a decrease in circulating endothelial cell levels, indicating potential benefits for vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease. Wu, SC., Pollak, R., Frykberg, RG., et al.[2021]

Citations

1. internationaljournaloftissuerepair.com internationaljournaloftissuerepair.com/index.php/ijtr/article/view/35

Evaluation of single layer amniotic membrane in the ... Evaluation of single layer amniotic membrane in the management of nonhealing diabetic foot ulcers: an interim analysis of CAMPX. Authors. Thomas ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11032220/

Assessing the Application and Effectiveness of Human ... Findings revealed that HAM treatment significantly accelerated ulcer closure, demonstrating over 90% complete healing compared to standard care.

3. bmcsurg.biomedcentral.com bmcsurg.biomedcentral.com/articles/10.1186/s12893-021-01084-8

Systematic review on the rational use of amniotic membrane ... This study aimed to evaluate the current scientific evidence on effectiveness of use of amniotic membrane in healing the diabetic foot ulcers.

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

Study Details | NCT07078968 | A REAL WORLD DATA ... A REAL WORLD DATA COLLECTION OF HUMAN AMNIOTIC MEMBRANE(S) ON DIABETIC FOOT ULCERS, VENOUS LEG ULCERS, PRESSURE ULCERS AND POST OPERATIVE WOUNDS.

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7885244/

Systematic review on the rational use of amniotic membrane ... The current studies using amniotic membrane allografts give reliable evidence of reduction in healing time over conventional methods.

7. 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 Grafix® for the treatment of chronic diabetic foot ulcers: Results of a multi-centre, controlled, randomised, blinded ...

8. 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 ...