Assessment of the Efficacy and Tolerance of Sub-cutaneous Re-injection of Autologous Adipose-derived REGEnerative Cells in the Local Treatment of Neuropathic Diabetic Foot ulcERs (REGENDER)

Assessment of the Efficacy and Tolerance of Sub-cutaneous Re-injection of Autologous

Diabetic foot ulcer (DFU) is a major complication and the leading cause of hospitalization among people with diabetes mellitus. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations. Despite many therapeutic advances over the past decades, including dressings (hydrocolloids, alginate, skin substitutes) and growth factors, healing rates of DFU remain low.

Mechanisms of faulty wound healing in diabetic patients are complex, related to both intrinsic and extrinsic factors. The main reasons for impaired healing appears to be: 1/exhaustion of local cell populations that promote wound healing; 2/excessive production of matrix metalloproteases (MMPs) coupled with reduced expression of the tissue inhibitors of MMPs; 3/impaired neovascularisation coupled with reduced numbers of endothelial progenitor cells and impairment of their functioning. These imbalances may result in excessive degradation of extracellular matrix components, as well as an inappropriate local inflammatory response .

Adipose-derived stroma vascular fraction provides a rich and easily accessible source of autologous cells for regenerative medicine applications. Il contains multipotent stem cells and progenitors called adipose-derived regenerative cells (ADRCs) able to stimulate wound healing. There are attracted to the wound site where they supplement the wound bed with similar cell types, secrete numerous growth factors and cytokines, increase macrophage recruitment, enhance granulation tissue, and improve vascularisation . The reparative capabilities coupled with good safety of ADRCs have been illustrated in a study for treating severe and irreversible radiation-induced lesions, and in a study for treating sclerodactyly in patients with diffuse scleroderma. Numerous case reports showing healing of refractory wounds following treatment with autologous ADRCs have also been reported.

Based on these previous reports, the present study aims to assess the efficacy and tolerance of injection of ADRCs for the local treatment of neuropathic or neuro-ischemic DFU.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: adipose-derived regenerative cells (ADRCs)

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: PATRICE DARMON; Phone Number: +33491383653; Email: patrice.darmon@ap-hm.fr
• Study Contact Backup: Name: alexandra GIULIANI; Phone Number: +33491382747; Email: alexandra.giliani@ap-hm.fr

Study Locations

• France
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille
    • Contact: PATRICE DARMON; Email: patrice.darmon@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient older than 18
• Patient with type 1 or 2 diabetes mellitus with HbA1C level < 10%
• Patient with diagnosis of neuropathic or neuro-ischemic DFU
• Grade 1 or 2 ulcer on the Wagner scale
• Ulcer with a surface area comprised between 1 cm2 and 15 cm2 at day 0 Patient present for a minimum of 4 weeks under the current investigator's care including adequate wound debridement and offloading
• Semmes-Weinstein monofilament test indicating neuropathy
• DFU located on the toe or on the lateral, dorsal surface of the forefoot or heel

Exclusion Criteria:

• Pregnant or likely to become pregnant or breast feeding woman
• Critical ischemia of the target limb, defined by pain at rest and an ankle systolic pressure < 50 mm Hg, or a toe systolic pressure < 30 mm Hg
• Surgery or surgical revascularisation < 2months
• Decrease or increase in the ulcer size by 30% or more within a 2-wk run-in period
• DFU clinically infected as defined by the IDSA/IWGDF criteria, osteomyelitis confirmed by MRI, or other evidence of infection is present Dossier LIC-15-15-0005 REGENDER Déposé le 09/03/2015 15:22:11 par M. Patrice DARMON Appel LIC-15-2015 Page 3 sur 6
• Patient who cannot bear an off-loading method
• Patient with an active neoplasm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetic foot ulcer	Drug: adipose-derived regenerative cells (ADRCs); injection of the experimental treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving 100% wound closure	20 WEEKS

Secondary Outcome Measures

Outcome Measure	Time Frame
time to reach complete wound closure	20 WEEKS
wound surface regression in relative value	20 weeks
wound surface regression in absolute value	20 weeks
percentage of patients achieving 50 % wound closure	20 weeks
ulcer recurrence rate	20 weeks
change in quality of life assessed by the SF-36 QoL survey from baseline	20weeks

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: PATRICE DARMON, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer
• Other Study ID Numbers: 2016-41

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No