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Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia. (ACellDREAM2)

Primary Purpose

Critical Limb Ischemia and Peripheral Artery Disease

Status

Terminated

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Autologous ASC (for Adipose-derived Stem/Stroma Cell)

About this trial

This is an interventional treatment trial for Critical Limb Ischemia and Peripheral Artery Disease focused on measuring Cell therapy, ASC autologous, CLI, PAD, No option

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients over 18 years old,
Rest pain or ischemic ulcers /gangrene of the lower limb, present for at least 15 days, requiring analgesic absorption, with ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg

Patient with persistent CLI after revascularization will be included if :

they have severe cardiac, respiratory or renal disease who are at increased risk of complication from surgery or anesthesia, e.g. moderately severe or severe heart failure (NYHA class III or IV), severe or very severe Chronic Obstructive Pulmonary disease or severe renal disease (creatinine clearance <30 mL/minute).
OR
there is no option for endovascular or open surgery revascularization ; or poor option (defined by: need for an infra-popliteal by-pass without the availability of autologous great saphenous vein, need for use of great saphenous vein <3 mm in diameter for tibial level bypass based on venous duplex ultrasound, or calcified or small (<2 mm) distal target vessel, or open wound on the receiving site or infrapopliteal PAD)
- Patients who signed the informed consent,
- Patient affiliated to a social security system

Exclusion Criteria:

History of cancer
Need of a major amputation (amputation at or above the ankle) within 2 weeks,
Ulcers with exposure of tendons, osteomyelitis, or clinically uncontrolled infection,
TcPO2 <10 mmHg at rest and < 30 mmHg sitting with legs dependent (very poor vascular reserve),
Patient under judicial protection,
Pregnant women,
Women of childbearing age without effective contraception.
Refusal of the patient to participate in the study,
Positive HIV-1 or 2, Human T Leukemia virus (HTLV)-1 or 2, Hepatite B Virus (HBV) (except vaccine profile), Syphilis (except inactive disease), or Hepatite C Virus (HCV)
Patients necessitating drugs with inhibitory or stimulatory effect on the growth and multiplication of cells or drugs with immunosuppressive effect: Cyclosporine, Mycophenolate mofetil, Azathioprine, Tacrolimus (systemic), Anthracyclines, Neupogen or equivalent, Etanercept, Interferons, Corticoids at anti-inflammatory doses.
No possibility of adipose tissue harvest and cell injection in the leg
Another clinical trial participation (except non interventional studies),
Patient under judicial protection,
Pregnant and breastfeeding women,
Women of childbearing age without effective contraception,
Lack in understanding the nature and aims of the study and/or difficulties in communication with the investigator.

Sites / Locations

Rangueil Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ASC (Adipose-derived Stem/Stroma Cells)

Arm Description

Patients administrated with autologous ASC in their ischemic inferiors limbs

Outcomes

Primary Outcome Measures

Number of patients alive without major amputation

Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.

Number of patients alive without critical limb ischemia

Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.

Secondary Outcome Measures

New vessels

Blind evaluation of the number of new vessels in the treated limb by standardized angiographic magnetic resonance

Blood flow

Evaluation of the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure.

Wound surface reduction

Percentage reduction of wound surface (standardized layer measurement).

Ulcer healing

Evaluation of percentage of complete ulcer healing.

Pain reduction

Evaluation of pain reduction by standardized evaluation (visual scale and drug consumption). The visual scale is in a form of plastic ruler and measures the intensity of pain on a scale ranging from 0 (no pain) to 10 (maximum pain).

Wound infection

Percentage of wound infection and irritative dermatitis (expected adverse events)

Immuno measures in blood sample

interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα), will be measured out in blood samples.

Immuno measures in vitro

Mesenchymal stem cells (MSC) trophic factors and immune- modulators (Hepatocyte growth factor (HGF), Vascular Endothelial Growth Factor (VEGF), indoleamine 2, 3-dioxygenase (IDO), Human Leucocyte Antigen G (HLA-G)) will be studied in vitro.

Full Information

NCT ID

NCT03968198

First Posted

May 14, 2019

Last Updated

March 29, 2023

Sponsor

University Hospital, Toulouse

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Etablissement Français du Sang

1. Study Identification

Unique Protocol Identification Number

NCT03968198

Brief Title

Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia.

Acronym

ACellDREAM2

Official Title

Autologous Transplantation of Adipose Tissue Derived Mesenchymal Stroma/Stem Cells (ASC) in Patients With Critical Limb Ischemia.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

organizational difficulties for the collection of adipose tissue and for the supply of the experimental drug

Study Start Date

March 4, 2020 (Actual)

Primary Completion Date

March 10, 2023 (Actual)

Study Completion Date

March 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Etablissement Français du Sang

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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. The investigators already shown in a phase I study, that adipose derived mesenchymal cells injected in patients with critical limb ischemia and no option for revascularization, had a very good tolerance and interesting effects on skin oxygenation and healing. The aim of the present clinical trial is to confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization.

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, 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. Current research is focusing on the development of cell-based therapies using different sources of stem cells which can provide revascularization and oxygenation of the tissues. A specific form of stem cells, called Adipose-derived Stem/Stroma Cells (ASC), has shown promise for recovering from ischemic disease like critical limb ischemia (CLI) in preclinical trial and trial in phase I. This study will confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization. This study is a phase II, prospective, multicentric, open trial and no comparative. A maximum of 43 patients will be included in two-stage to receive 90*106 intramuscular injection of ASC. Patients will be followed-up for 6 months. The primary endpoint is the number of patients alive without major amputation and without critical limb ischemia (defined as the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month). The secondary endpoints are to evaluate: the number of new vessels in the treated limb by standardized angiographic magnetic resonance the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure the percentage reduction of wound surface and percentage of complete ulcer healing the pain reduction by standardized evaluation (visual scale and drug consumption) the percentage of wound infection and irritative dermatitis (expected adverse events) interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα)measurements in blood samples Mesenchymal stem cells MSC trophic factors and immune- modulators (Hepatocyte growth factor (HGF), Vascular Endothelial Growth Factor (VEGF), indoleamine 2, 3-dioxygenase (IDO), Human Leucocyte Antigen G (HLA-G)) in vitro.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Limb Ischemia and Peripheral Artery Disease

Keywords

Cell therapy, ASC autologous, CLI, PAD, No option

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ASC (Adipose-derived Stem/Stroma Cells)

Arm Type

Experimental

Arm Description

Patients administrated with autologous ASC in their ischemic inferiors limbs

Intervention Type

Drug

Intervention Name(s)

Autologous ASC (for Adipose-derived Stem/Stroma Cell)

Intervention Description

After adipose tissue aspiration (liposuction) by an authorized person, ASCs were isolated and cultured during 14±2 days by the French Blood Establishment. Then, patients receive intramuscular injections of ASCs.

Primary Outcome Measure Information:

Title

Number of patients alive without major amputation

Description

Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.

Time Frame

Between 1 and 6 months

Title

Number of patients alive without critical limb ischemia

Description

Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.

Time Frame

Between 1 and 6 months

Secondary Outcome Measure Information:

Title

New vessels

Description

Blind evaluation of the number of new vessels in the treated limb by standardized angiographic magnetic resonance

Time Frame

Between 1 and 6 months

Title

Blood flow

Description

Evaluation of the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure.

Time Frame

Between 1 and 6 months

Title

Wound surface reduction

Description

Percentage reduction of wound surface (standardized layer measurement).

Time Frame

Between 1 and 6 months

Title

Ulcer healing

Description

Evaluation of percentage of complete ulcer healing.

Time Frame

Between 1 and 6 months

Title

Pain reduction

Description

Time Frame

Between 1 and 6 months

Title

Wound infection

Description

Percentage of wound infection and irritative dermatitis (expected adverse events)

Time Frame

Between 1 and 6 months

Title

Immuno measures in blood sample

Description

interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα), will be measured out in blood samples.

Time Frame

Between 1 and 6 months

Title

Immuno measures in vitro

Description

Time Frame

Between 1 and 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients over 18 years old, Rest pain or ischemic ulcers /gangrene of the lower limb, present for at least 15 days, requiring analgesic absorption, with ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg Patient with persistent CLI after revascularization will be included if : they have severe cardiac, respiratory or renal disease who are at increased risk of complication from surgery or anesthesia, e.g. moderately severe or severe heart failure (NYHA class III or IV), severe or very severe Chronic Obstructive Pulmonary disease or severe renal disease (creatinine clearance <30 mL/minute). OR there is no option for endovascular or open surgery revascularization ; or poor option (defined by: need for an infra-popliteal by-pass without the availability of autologous great saphenous vein, need for use of great saphenous vein <3 mm in diameter for tibial level bypass based on venous duplex ultrasound, or calcified or small (<2 mm) distal target vessel, or open wound on the receiving site or infrapopliteal PAD) Patients who signed the informed consent, Patient affiliated to a social security system Exclusion Criteria: History of cancer Need of a major amputation (amputation at or above the ankle) within 2 weeks, Ulcers with exposure of tendons, osteomyelitis, or clinically uncontrolled infection, TcPO2 <10 mmHg at rest and < 30 mmHg sitting with legs dependent (very poor vascular reserve), Patient under judicial protection, Pregnant women, Women of childbearing age without effective contraception. Refusal of the patient to participate in the study, Positive HIV-1 or 2, Human T Leukemia virus (HTLV)-1 or 2, Hepatite B Virus (HBV) (except vaccine profile), Syphilis (except inactive disease), or Hepatite C Virus (HCV) Patients necessitating drugs with inhibitory or stimulatory effect on the growth and multiplication of cells or drugs with immunosuppressive effect: Cyclosporine, Mycophenolate mofetil, Azathioprine, Tacrolimus (systemic), Anthracyclines, Neupogen or equivalent, Etanercept, Interferons, Corticoids at anti-inflammatory doses. No possibility of adipose tissue harvest and cell injection in the leg Another clinical trial participation (except non interventional studies), Patient under judicial protection, Pregnant and breastfeeding women, Women of childbearing age without effective contraception, Lack in understanding the nature and aims of the study and/or difficulties in communication with the investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

BURA-RIVIERE Alessandra, PhD

Organizational Affiliation

Toulouse University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rangueil Hospital

City

Toulouse

ZIP/Postal Code

31059

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia.

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