Clinical Utility of an Amniotic Membrane Allograft for Diabetic Foot Ulcer Wound Management (REBOUND)

A Prospective, Post-market Randomized Controlled Trial (RCT) to Demonstrate Clinical Utility of an Amniotic Membrane Allograft in Diabetic Foot Ulcer (DFU) Wound Management

The goal of this clinical trial is to learn if use of Orion™, a dual-layer amniotic membrane allograft, in addition to standard wound care treatment can improve patient outcomes for people over the age of 50 with diabetic foot ulcers. The study aims to determine the incidence of complete wound closure at the end of 12 weeks of treatment. Researchers will compare the outcomes between a group of people treated with standard wound care and another group treated with standard wound care in addition to the amniotic membrane allograft to see if the amniotic membrane allograft improves wound healing.

During the study, participants will visit their doctor weekly over a 12 week period, which is standard for diabetic foot ulcer treatment procedures, and fill out a questionnaire measuring quality of life.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Device: Orion TM Amniotic Membrane Allograft; Procedure: Standard of Care (SOC)

Detailed Description

Lower extremity diabetic ulcers are a common complication affecting millions of people in the United States. The purpose of this study is to evaluate the clinical utility of Orion™, a dual-layer amniotic membrane allograft, versus standard wound care in the management of diabetic foot ulcers. Amniotic membrane allografts are confirmed by the FDA Tissue Reference Group to meet the criteria for regulation solely under Section 361 of the PHS Act as defined in 21 CFR Part 1271 for the management of diabetic foot ulcers. Investigators hypothesize that the group of participants who receive amniotic membrane allografts in addition to standard wound care will experience a faster rate and higher incidence of complete wound closure compared to standard wound care alone. For only partially healed wounds, investigators anticipate a statistically significant reduction in the size of the ulcer and improved quality of life for participants in the experimental arm compared to standard wound care alone.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Schultz, BS, CCRA, ACRP-PM; Phone Number: 719-400-7463; Email: cschultz@ecr-inc.com
• Study Contact Backup: Name: Cyaandi Dove, DPM; Phone Number: 210-567-5135; Email: dovec@ohsu.edu

Study Locations

• United States
  • California
    • Palm Springs, California, United States, 92262
      • Recruiting
      • DPMG
      • Principal Investigator: Gemma Kim, MD
      • Contact: Dario Kuzmanovic, MHSc; Phone Number: 909-547-7178; Email: dario.kuzmanovic@dpmghealth.com
    • San Francisco, California, United States, 94115
      • Recruiting
      • Center for Clinical Research Inc.
      • Principal Investigator: Alexander Reyzelman, DPM
      • Contact: Gayana Sarkisova; Phone Number: 800-363-1069; Email: gayana@ccr-trials.com
    • Vista, California, United States, 92081
      • Recruiting
      • ILD Research Center
      • Principal Investigator: Dean J. Vayser, DPM
  • Connecticut
    • Darien, Connecticut, United States, 06820
      • Recruiting
      • Stamford Health Medical Group
      • Contact: Kaila Lasher; Phone Number: 203-276-4787; Email: klasher@stamhealth.org
      • Principal Investigator: Rachel Albright, DPM, MPH
  • Florida
    • Pembroke Pines, Florida, United States, 33025
      • Recruiting
      • Optimum Care Research Center
      • Contact: Daniel Moran; Phone Number: 954-854-5485; Email: d.moran@optimumcareresearch.com
      • Principal Investigator: Ronoel Penalver, MD
  • Illinois
    • Chicago, Illinois, United States, 60064
      • Recruiting
      • Rosalind Franklin University of Medicine and Science
      • Contact: Jacque Ortiz; Phone Number: 847-578-8243; Email: jacquelin.ortiz@rosalindfranklin.edu
      • Principal Investigator: Stephanie Wu, DPM
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Recruiting
      • Chesapeake Research Group
      • Contact: Samantha Mallicote; Phone Number: 410-761-0115; Email: smallicote@crgmd.com
      • Principal Investigator: Ira J Gottlieb, DPM
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Melanie Abrahamson-Sommer; Phone Number: 917-610-3005; Email: abrahamm@ohsu.edu
      • Principal Investigator: Cyyandi Dove, DPM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Ambulatory patients ≥ 50 and ≤ 85 years of age;
2. Willing and able to provide informed consent;
3. Willing and able to comply with study requirements;
4. Presence of Wagner 1 and superficial Wagner 2 DFU extending at least through the dermis provided the DFU is located in the foot distal to the medial malleolus
5. If multiple Wagner 1 and superficial Wagner 2 DFUs are present, the largest ulcer meeting DFU eligibility criteria will be selected as the index DFU in the study;
6. Index ulcer is able to be visualized and accurately measured with eKare Insights;
7. Non-study ulcers must be > 2 cm (.79 in.) from the index ulcer;
8. Index DFU identified ≥ 4 weeks prior to study screening and < 52 weeks from the date of informed consent;
9. Index DFU area > 1.0 cm2 (0.39 in.) and < 25 cm2 (9.84 in.) at screening and at Wound Management Period Visit #1;
10. Index DFU offloaded according to SOC for entire run-in period, prior to randomization;
11. Potential participant is under the care of a clinician for diabetic management and other medical conditions (the site PI may assist/direct the patient in the pre-screening period to obtain a PCP).
12. Index foot has adequate circulation defined as meeting one (1) of the following within 30 days of screening:

A. ABI ≥ 0.7 and ≤ 1.3 AND TBI > 0.7; B. Dorsum transcutaneous oxygen tension measurement (TcPO2) ≥ 40 mmHg; C. Arterial duplex with biphasic flow in BOTH the DP and PT arteries verified by PI and documented.

Exclusion Criteria

1. Index foot ulcer documented to be caused by a medical condition other than diabetes;
2. Potential subject has five (5) or more DFUs and/or VLUs in the target limb;
3. DFU is secondary to Charcot neuroarthropathy;
4. Treatment with an antibiotic impregnated primary dressing ≤ 4 weeks prior to study screening;
5. Index ulcer is potentially or confirmed by biopsy to be cancerous;
6. Index ulcer site has undergone radiation therapy;
7. Venous leg ulcers in diabetic patients;
8. Active infection proximal to or at site of index ulcer;
9. Index foot ulcer reduced in area by ≥ 20% at the end of the 4-week run-in period;
10. Presence of active osteomyelitis or bone infection as verified by x-ray /MRI within 30 days of visit #1 of the run-in period;
11. Raynaud's disease;
12. Unreconstructible arterial ischemia which may lead to nonhealing;
13. Treatment with immunosuppressants, including systemic corticosteroids for ≥ 2 weeks within 30 days prior to study screening, or are anticipated during study participation;
14. Any active cancer undergoing treatment ≤ 30 days prior to wound management visit #1 of the run-in period, or is anticipated during study participation;
15. Treatment with chemotherapy within 30 days of the first study wound management visit of the run-in period, or is anticipated during study participation;
16. Diabetics with poor metabolic control, defined as HbA1c ≥ 12.0%, within 30 days of visit #1 of the run-in period;
17. Participation in an investigational device, biologic, or drug study currently or within 30 days of study wound management visit #1 of the run-in period;
18. Prior use of any advanced skin substitute product on the index ulcer within 60 days of visit #1 of the run-in period;

19. Index ulcer was continued to be treated after visit #1 of the run-in period and/or anticipate treatment during study participation with any of the following prohibited therapies:

    1. Biomedical or topical growth factor;
    2. Topical steroids applied to the index ulcer surface;
    3. On medications that are considered immune system modulators that could affect graft incorporation;
    4. Scarlet red dressing;
    5. Dakin's solution;
    6. Mafenide acetate;
    7. Tincoban;
    8. Zinc sulfate;
    9. Povidone-iodine solution;
    10. Polymyxin/nystatin;
    11. Chlorhexidine;
20. Patient is taking a cyclooxygenase-2 inhibitor (COX-2 inhibitor); such as, celecoxib (Celebrex, Consensi, Elyxyb), valdecoxib (Bextra), amlodipine (Consensi);
21. Patient has serum creatinine > 2.5 mg/dL within 30 days of study wound management visit #1 of the run-in period;
22. Autoimmune connective tissue disease;
23. End stage renal disease (ESRD);
24. Presence of any condition which would seriously compromise the subject's ability to complete this study;
25. Known history of poor adherence to medical therapy and/or clinic appointments;
26. Pregnant, or planning to become pregnant during the study;
27. Life expectancy < 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care (SOC); Standard of care DFU wound management	Procedure: Standard of Care (SOC); Standard wound care entails surgical debridement as needed to remove all non-viable tissue, screening for infection and probing of the wound for bone, weekly application of a collagen alginate primary dressing, and off-loading using a removable diabetic offloading cam-walker or total contact cast.
Experimental: Amniotic Membrane plus Standard of Care; Weekly application of Orion™ amniotic membrane allograft in addition to standard of care DFU wound management	Device: Orion TM Amniotic Membrane Allograft; The intervention is a sterile allograft made from dehydrated extracellular matrix, designed to promote wound healing by providing a reliable and protective wound covering. Amniotic membranes are hypothesized to promote healing in open wounds by serving as a scaffold to support native tissue ingrowth, encouraging angiogenesis, and limiting microbial spread.; Procedure: Standard of Care (SOC); Standard wound care entails surgical debridement as needed to remove all non-viable tissue, screening for infection and probing of the wound for bone, weekly application of a collagen alginate primary dressing, and off-loading using a removable diabetic offloading cam-walker or total contact cast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Complete Wound Closure	Percentage of enrolled study participants demonstrating 100% re-epithelialization of the index wound without leaking exudate at 12 weeks post-randomization.	starting from randomization until last visit of the 12-week wound management period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life metrics	Change in QoL metrics at twelve (12) weeks post-randomization compared to baseline as reported by the subject in the WOUND-Q QoL questionnaires: Life Impact (8-32; higher is better); Lower Limb Symptoms (10-40; higher is better)	starting from randomization to last visit of the 12-week wound management period
Recurrence Within Six Months	Recurrence within six (6) months post wound managment period completion, defined as meeting the primary endpoint and reopening of index ulcer at the same site within six (6) months.	starting from last visit of the 12-week wound management period until 6-month follow-up visit
Time to complete wound closure	time to 100% re-epithelialization of the index ulcer without leaking exudate as assessed by Kare inSight®, starting at randomization through identification of complete wound closure.	From time of randomization until the end of the twelve (12) week Wound Management Period.
Incidence of complete wound closure	Incidence of complete wound closure, defined as 100% re-epithelialization of the index ulcer without leaking exudate as assessed by eKare inSight® at eight (8) weeks post-randomization.	From time of randomization to eight (8) weeks post-randomization.
Number of Orion™ Allografts or collagen alginate (SOC) dressings required for complete wound closure.	The number of Number of Orion™ Allografts or collagen alginate (SOC) dressings required for complete wound closure during twelve (12) week Wound Management Period.	From the time of randomization through the twelve (12) week Wound Management Period.
Change in QoL metrics in follow-up.	Change in QoL metrics to six (6) months after completion of the Wound Management Period as reported by the patient in the WOUND-Q QoL questionnaire.	From time of completion of the Wound Management Period through six (6) months.
Adverse events	Adverse events from randomization through six (6) month follow-up.	From the time of randomization through six (6) month follow-up.
Serious adverse events	Occurrence of serious adverse events (SAEs) from randomization through six (6) month follow-up.	From the time of randomization through six (6) month follow-up.
Major amputations	Major amputations defined as amputation above the metatarsals.	From the time of randomization through six (6) month follow-up.
Minor amputations	Minor amputations defined as amputation involving toe or metatarsal only.	From the time of randomization through six (6) month follow-up.
Hospital admission(s)	Hospital admission(s) and diagnosis from randomization through six (6) month follow-up.	From the time of randomization through six (6) month follow-up.
Emergency Department (ED) visit(s)	ED visit(s) without admission through six (6) month follow-up.	From the time of randomization through six (6) month follow-up.
Change in wound size	Percent area change of index ulcer at completion of twelve (12) weeks post-randomization.	from the time of randomization through twelve (12) weeks post-randomization.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per-Patient Product Cost	Per-patient product cost for Orion™ Allografts during the course of wound management.	starting from randomization until last visit of the 12-week wound management period.
Number of wound management products used.	Number of wound management products used in each group.	Following completion of the 12-week Wound Management Period (WMP Visit #13) through the six (6) month follow-up.

Collaborators and Investigators

• Sponsor: Legacy Medical Consultants

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: DFU; diabetic foot ulcer; amniotic membrane allograft
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Skin and Connective Tissue Diseases; Diabetic Foot; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: LEGA-CLIN-2024-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No