Safety and efficacy of umbilical cord-derived mesenchymal stem cells treatment for patients with Critical Limb Ischemia
- Conditions
- Critical Limb Ischemia.Critical Limb IschemiaG173.9
- Registration Number
- IRCT20211021052828N2
- Lead Sponsor
- Rasht University of Medical Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 5
Aged 18–60 years
patients with Type I or II diabetes, established more than one year ago
Glycosylated hemoglobin (HbA1c) < 8%
Patients suffering from infrapopliteal occlusive disease with rest pain and ischemic ulcer/necrosis, who are not eligible for or have failed traditional revascularization treatment as per the investigators judgment (No option patients)
Subjects with poor or norevascularization option (surgical or endovascular) classified as CLI Rutherford Category III-5 or Patients in Rutherford- III-6 as the gangrene extends maximally up to the metatarsal head but limited to toes (Patients with wet gangrene must undergo wound debridement/amputation before screening). For these patients, one of the following options must be confirmed and documented at screening: Ankle systolic pressure < 70 mmHg, systolic toe pressure < 50 mmHg, poor or no revascularization option, since the revascularization using surgical or endovascular methods are not feasible in the investigator opinion due to the anatomy of existing vessels and/or existing comorbidity and/or previously failed surgical or endovascular revascularization.
Advanced CLI with major tissue loss due to the significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads
CLI Rutherford Category 4
Subjects with arterial insufficiency in the lower limb as a result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (both limited and diffuse forms))
Clinical evidences of invasive infection on the targeted leg with the major tissue loss in the mid-foot or heel involving tendon and/or bone, and/or when intravenous antibiotics are required to treat the infection according to the Investigator
At screening, the presence of only neuropathic ulcers on the targeted leg
Amputation at the talus or above parts of the targeted leg
major amputation within the first month after randomization
Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
platelet count < 50,000/µL
International normalized ratio (INR) > 1.5 for patients on anticoagulant medication .INR > 1.5 is allowed when the Investigator and the haematologist consider the patient eligiblity for BM collection.
Evidence of moderate to severe hepatocellular dysfunction according to the physician
Subjects who may not be healthy enough to successfully complete all protocol requirements including BM collection, or who are not expected to survive more than 12 months. For example: a. Concurrent severe congestive heart failure (New York Heart Association Classes III and IV). b. Patients with the left ventricular ejection fraction < 35%. c. Life-threatening ventricular arrhythmias, unstable angina (characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration), and/or myocardial infarction within four weeks before screening. d. Coronary artery bypass grafting or percutaneous coronary intervention within one month before screening. e. A renal and/or carotid revascularization procedure within one month of screening. f. Transient ischemic attack within three months prior to screening. g. Deep vein thrombosis within three months prior to screening. h. Subjects with immunocompromised conditions, organ transplant recipients and/or subjects in need of immunosuppressive therapy. i. neurodegenerative disease such as Alzheimer disease
Subjects who participate in another clinical interventional trial
Patients who are contraindicated for MRA
Patients with deep vein thrombosis in any limb
Documented terminal illness or cancer or any concomitant disease process with a life expectancy of <1 year
History of severe alcohol or drug abuse within 3 months of screening
Hb < 10 gm% for males, Hb% < 9 gm% for females, serum creatinine = 2mg%, Total serum Bilirubin =2mg%
Pregnant and lactating women
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Wound healing extent. Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: Square centimeters.;Temperature changes. Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: Thermography.;Peripheral pulses. Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: Palpation.;Pain on the Visual Analogue Scale (VAS). Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: Examination.
- Secondary Outcome Measures
Name Time Method Ankle–brachial index. Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: The ABI is performed by measuring the systolic blood pressure from both brachial arteries and from both the dorsalis pedis and posterior tibial arteries after the patient has been at rest in the supine position for 10 minutes.;Reduced limb amputation. Timepoint: 1, 2, 3 months after implantation of stem cells. Method of measurement: Observation.;Collateral blood vessels angiogenesis. Timepoint: One, 2, 3 months after implantation of stem cells. Method of measurement: Magnetic resonance angiogram (MRA).;CT Angiography. Timepoint: Before intervention and 1, 2, 3 months after implantation of stem cells. Method of measurement: X-Ray.