Tolerance Study of Allogeneic of Adipose Tissue Derived Mesenchymal Stroma/stem Cells (AdMSC) Transplantation in Patients with Critical Limb Ischemia. (AlloDREAM)

Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD). Cell therapy delivered to the ischemic muscle constitutes a promising approach to treat CLI patients with no or poor options of vascularization. Pre-clinical study and clinical phase I have demonstrated the safety and feasibility of the use of autologous AdMSC treatment in patients without option for revascularization CLI patients and encouraging preliminary efficacy results have been highlighted in the pilot phase. In order to optimize AdMSC quality and to accelerate treatment availability researchers decide to test the use of allogeneic cryopreserved AdMSC from healthy donor. The aim of this phase I study is to evaluate the safety of allogeneic AdMSC injection in ischemic leg.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: Adipose tissue derived mesenchymal Stroma/stem Cells transplantation

Detailed Description

Lower limbs arteries are a frequent localization of atheroma in elderly people (15-20% after 70 years). The most severe stage of the disease, critical limb ischemia (CLI), defined clinically by the presence of rest pain or ischemic ulcer with an ankle pressure <50 mmHg or a toe pressure <30 mmHg or a TcPO2 <30 mmHg, has a dramatic prognosis at 12 months, with 30% of the patients alive with an amputation, 20% mortality and only 20% of patients with a resolved disease, independently from the treatment. The only validated treatment for this disease is revascularization by endovascular procedures or open surgery. Patients with no option or poor option (high risk) for revascularization have the worst prognosis. Regenerative medicine has been studied in this field, by the injection of bone marrow derived stem cells in the ischemic limb to improve neo-angiogenesis. Despite the encouraging first results, few studies have shown a clinical interest of this kind of approach. The products tested were heterogeneous compounds derived from the bone marrow.

Different types of stem cells have recently been studied in clinical trial on ischemic disease of the heart and muscular arteries. Adipose derived stem cell, have shown in vitro and in vivo models a stronger potential of success in recovering from ischemic disease and oxygenation of the tissues.

Scientists already shown in a phase I study, that adipose derived mesenchymal cells injected in patients with CLI and no option for revascularization, had a very good tolerance and interesting effects on skin oxygenation and healing.

In order to optimize the quality of the AdMSC, to avoid the abdominal sample under anesthesia in the already suffering patients and to have the cellular product available quickly, without waiting the 15 days of culture, researchers envisage the use of AdMSC of allogeneic origin taken from healthy donors and cryopreserved after culture. Indeed, the results of phase 1 of ACellDREAM showed that almost half of the patients suffering from IC had to be amputated during the 15 days of culture. Preliminary experiments show that the phenotypic characteristics, in vitro properties and in vivo biodistribution of these cells after freezing are unchanged.

Researchers are planning a single phase, phase I study to evaluate the tolerability of intramuscular injection of allogeneic AUC in patients with critical non-revascularizable ischemia, or with persistent ischemia despite revascularization.

The aim of this phase I is to evaluate safety of allogeneic AdMSC transplantation in patients with critical limb ischemia with poor options or no option for revascularization. Ten patients will be included and have AdMSC injection in their ischemic leg. Patients will be follow-up during six months to evaluate ulcer evolution, wound healing, pain, blood flow and immune response in blood samples.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: François-Xavier LAPEBIE, Dr; Phone Number: +33 5 61 32 24 38; Email: lapebie.fx@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • CHU Toulouse
    • Contact: François Xavier LAPEBIE, MD; Phone Number: +33 0561322638; Email: lapebie.fx@chu-toulouse.fr
    • Contact: François-Xavier LAPEBIE, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients over 18 years old,
• Patients with CLI according international definition: 1) rest pain of ischemic origin or ischemic trophic disorder present for at least 15 days, and 2) an ankle pressure ≤50 mmHg (≤70 mmHg for diabetic patients) or a toe pressure ≤30 mmHg or a TcPO2 ≤30 mmHg,
• Patient not revascularizable by decision of the surgeon or anesthesiologist orpatient with persistent critical ischemia after revascularization,
• Patient with a life expectancy greater than 6 months,
• Patients who signed the informed consent,
• Women of childbearing age with effective contraception (oral contraception, IUD, dermal implant) and with negative pregnancy test,
• Patient affiliated to a social security system.

Exclusion Criteria:

• Need of a major amputation (amputation at or above the ankle) within 1 month following the inclusion,
• Another clinical trial participation (except observational studies),
• Patient with active cancer history in the 5 previous years except cured basal cell carcinoma or cured low-stage melanoma,
• Patient allergic to local anesthetics
• Immunosuppressive therapy
• Ulcers with exposure of tendons, osteomyelitis, or clinically uncontrolled infection,
• Patient under the protection of justice or under guardianship or curatorship.

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: CellReady; All the patients will be included and will have AdMSC injections (CellReady®) in their ischemic led. They will be follow-up during 6 months.	Drug: Adipose tissue derived mesenchymal Stroma/stem Cells transplantation; Allogeneic adipose tissue-derived stromal cells (AdMSC) (CellReady ® drug) will be administered intramuscularly into the ischemic limb (dose of 90x10^6 AdMSC) of patients. They will be followed at 1 day, 7 days, 30 days, 90 days, and 180 days after the injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the tolerance	local and systemic tolerance during 6 months by the collection and analysis of adverse events (serious or non-serious) throughout the duration of the study	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the efficacy of the treatment on critical limb ischemia.	Proportion of patients without criteria of CLI	Day 30, Day 90, and Day 180
Evaluation of the evolution of ischemia objective parameters.	Pressures, laser-Doppler and TcPO2	Day 0, Day 30, Day 90, and Day 180
Evaluation of the healing.	Number of complete scarring	Day 30, Day 90, and Day 180
Evaluation of the proportion of patients who required a major amputation.		Day 180
Evaluation of the pain Evolution	VAS (visual analogue scale), consumption of morphine or non-morphine analgesics	Day 0, Day 7, Day 30, Day 90, and Day 180
Evaluation of the neovascularization on the treated leg.	Determination of the number of neo-vessels formed by angiography, angio Magnetic resonance imaging (MRI) or angio-scanner.	Day 30, Day 90, and Day 180
Evaluation of the proportion of patients included who had all the injections.		Day 0
Evaluation of the evolution of the quality of life	Claudication Scale (CLAU-S®)	Day 0, Day 30, Day 90, and Day 180
Evaluation of the security.	Description of all adverse reaction during the trial	Day 0, Day 1, Day 7, Day 30, Day 90, and Day 180
Evaluation of the immunomodulatory activity of the injected cells.	- Immuno-monitoring by evaluation of the different circulating immune populations (Th1, Th2, Th17, Treg ...) associated with functional tests in vitro and immunological assays of pro and anti-inflammatory cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, TNFα, IFNγ).	Evaluated at Day 1, Day 7, Day 30, Day 90, and Day 180
Evaluation of the patient's immune response against Adipose-derived mesenchymal stem cells (AdMSCs)	Dosage of anti HLA (human leukocyte antigen) donor antobodies.	Day 30
Evaluation of the evolution of the quality of life.	EuroQol (EQ-5D-5L)	Day 0, Day 30, Day 90, and Day 180

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: François-Xavier LAPEBIE, Dr, Service de Médecine Vasculaire, Hôpital Rangueil, CHU de Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: cell therapy; Adipose tissue; allogeneic AdMSC
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia; Ischemia
• Other Study ID Numbers: RC31/21/0168; 2023-509312-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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