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

Trial Summary

What is the purpose of this trial?

A Randomized Controlled Multicenter Clinical Trial, Evaluating the Efficacy of a Single Layer Placental-based Allograft and Standard of Care versus Standard of Care alone in the management of Nonhealing 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.

What data supports the effectiveness of the treatment SLAM for diabetic foot ulcers?

Research shows that treatments using placental tissue, which contains stem cells and growth factors, have been effective in healing diabetic foot ulcers. Specifically, a study found that a cryopreserved placental membrane significantly reduced the occurrence of new or recurring foot ulcers and decreased mortality in diabetic patients compared to other treatments. ^{1 2 3 4 5}

Is placental-based treatment for diabetic foot ulcers safe for humans?

Research shows that placental-based treatments, like human amniotic membrane and cenplacel, are generally safe for humans. Studies found no significant difference in adverse events compared to standard care, and treatments were well tolerated with no serious side effects reported. ^{4 5 6 7 8}

How is the SLAM treatment for diabetic foot ulcers different from other treatments?

The SLAM treatment for diabetic foot ulcers is unique because it uses placental-derived products, which contain growth factors and mesenchymal stem cells that can promote healing. This approach is different from standard treatments as it focuses on enhancing the body's natural healing processes through these biological components. ^{1 2 3 4 9}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

Prospective study of cryopreserved placental tissue wound matrix in the management of chronic venous leg ulcers. [2020]

2. Netherlands 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. [2022]

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

Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Use of a dual-layer amniotic membrane in the treatment of diabetic foot ulcers: an observational study. [2022]

5. United States 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. [2023]

6. 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]

7. United States 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. [2023]

8. England 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A trial to determine the role of placental extract in the treatment of chronic non-healing wounds. [2004]