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Trial record 13 of 72 for:    stem cell peripheral arterial disease AND cell therapy

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

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ClinicalTrials.gov Identifier: NCT03968198
Recruitment Status : Not yet recruiting
First Posted : May 30, 2019
Last Update Posted : January 9, 2020
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Etablissement Français du Sang
Information provided by (Responsible Party):
University Hospital, Toulouse

Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date January 9, 2020
Estimated Study Start Date  ICMJE May 2020
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • Number of patients alive without major amputation [ Time Frame: Between 1 and 6 months ]
    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 [ Time Frame: Between 1 and 6 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2019)
  • New vessels [ Time Frame: Between 1 and 6 months ]
    Blind evaluation of the number of new vessels in the treated limb by standardized angiographic magnetic resonance
  • Blood flow [ Time Frame: Between 1 and 6 months ]
    Evaluation of the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure.
  • Wound surface reduction [ Time Frame: Between 1 and 6 months ]
    Percentage reduction of wound surface (standardized layer measurement).
  • Ulcer healing [ Time Frame: Between 1 and 6 months ]
    Evaluation of percentage of complete ulcer healing.
  • Pain reduction [ Time Frame: Between 1 and 6 months ]
    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 [ Time Frame: Between 1 and 6 months ]
    Percentage of wound infection and irritative dermatitis (expected adverse events)
  • Immuno measures in blood sample [ Time Frame: Between 1 and 6 months ]
    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 [ Time Frame: Between 1 and 6 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • New vessels [ Time Frame: Between 1 and 6 months ]
    Blind evaluation of the number of new vessels in the treated limb by standardized angiographic magnetic resonance
  • Blood flow [ Time Frame: Between 1 and 6 months ]
    Evaluation of the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure.
  • Wound surface reduction [ Time Frame: Between 1 and 6 months ]
    Percentage reduction of wound surface (standardized layer measurement).
  • Ulcer healing [ Time Frame: Between 1 and 6 months ]
    Evaluation of percentage of complete ulcer healing.
  • Pain reduction [ Time Frame: Between 1 and 6 months ]
    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 [ Time Frame: Between 1 and 6 months ]
    Percentage of wound infection and irritative dermatitis (expected adverse events)
  • Immuno measures [ Time Frame: Between 1 and 6 months ]
    interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα), will be measured out 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)) will be studied in vitro.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia
Official Title  ICMJE Autologous Transplantation of Adipose Tissue Derived Mesenchymal Stroma/Stem Cells (ASC) in Patients With Critical Limb Ischemia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Critical Limb Ischemia and Peripheral Artery Disease
Intervention  ICMJE Drug: Autologous ASC (for Adipose-derived Stem/Stroma Cell)
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.
Study Arms  ICMJE Experimental: ASC (Adipose-derived Stem/Stroma Cells)
Patients administrated with autologous ASC in their ischemic inferiors limbs
Intervention: Drug: Autologous ASC (for Adipose-derived Stem/Stroma Cell)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2019)
43
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 :

  1. 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

  2. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: BURA-RIVIERE Alessandra, PhD +33-5 61 32 24 38 ext 33 bura-riviere.a@chu-toulouse.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03968198
Other Study ID Numbers  ICMJE 14 7441 01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE
  • Institut National de la Santé Et de la Recherche Médicale, France
  • Etablissement Français du Sang
Investigators  ICMJE
Principal Investigator: BURA-RIVIERE Alessandra, PhD Toulouse University Hospital
PRS Account University Hospital, Toulouse
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP