Chronic critical limb ischemia
Conditions
Interventions
Optimal Recommended Dose Group (Phase II):Autologous mitochondrial transplantation (optimal recommended dose)
Control Group (Phase II):Standard drug therapy
Experimental Group 1 (Phase I):Autologous mitochondrial transplantation (5×10^5 mitochondria)
Control Group (Phase I):Standard drug therapy
Experimental Group 2 (Phase I):Autologous mitochondrial transplantation (1×10^6 mitochondria)
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Aged 18-80 years (inclusive), male or female; 2.Diagnosed with severe arterial ischemic disease of the extremities, reaching Rutherford class 4-5, i.e., ischemic rest pain, small-scale tissue defect, non-healing ulcer, etc.; 3.Within 1 month before enrollment, results of digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) confirm that one or more limb arteries have stenosis >=75% or occlusion; 4.Patients with vascular conditions unsuitable for open surgery and endovascular therapy, or those who have undergone open surgery and endovascular therapy but showed no improvement; 5.Patients whose limb ischemia has not been relieved after at least 1 month of conservative treatment (including regular drug therapy, smoking cessation, diet control and exercise therapy) before enrollment; 6.Female subjects of childbearing age and their male partners, as well as male subjects and their female partners, must agree to use effective contraceptive methods from 2 weeks before screening to 3 months after the end of drug administration; and have no plan to donate sperm/eggs.
Exclusion criteria
Exclusion criteria: 1. Those who have received cell transplantation, revascularization or sympathectomy within 4 weeks before enrollment (except for patients who have failed revascularization in the past 4 weeks); 2. Patients with acute limb ischemia; 3. Those who may undergo amputation within 4 weeks before enrollment, or those with aortic-iliac artery stenosis >=75% or occlusion; 4. Those who intend to observe limbs with serious infections (such as cellulitis, osteomyelitis, etc.), distal fascia or bone exposure; or with life-threatening complications; 5. Laboratory test results show: (1) Hemoglobin 2.0 upper limit of normal (ULN), alanine aminotransferase (ALT) >3ULN, aspartate aminotransferase (AST) >3ULN; 6. Those who meet any of the following virological test results: (1) Positive hepatitis B surface antigen (HBsAg) test, and hepatitis B virus deoxyribonucleic acid (HBV-DNA) quantification > the upper limit of normal value in the laboratory of the research center; (2) Hepatitis C virus antibody (HCV-Ab) test is positive, and the quantification of ribonucleic acid (HCV-RNA) of hepatitis C virus > the upper limit of normal value in the laboratory of the research center; (3) Treponema pallidum antibody (TP-Ab) positive; (4) Human immunodeficiency virus antibody (HIV-Ab) positive; 7. Those who have participated in any other clinical research (including clinical studies such as drugs and devices) and used investigational drugs or medical device interventions within 1 month (or within 5 half-lives, whichever is longer) before screening; 8. Those who have received live attenuated vaccines within 1 month before screening or plan to receive live attenuated vaccines during the study period; 9. Serious adverse events such as myocardial infarction, cerebral infarction, cerebral hemorrhage, pulmonary embolism, and severe abnormal liver and kidney function within 3 months before treatment; 10. Proliferative retinopathy and retinopathy examination cannot be performed, or ophthalmic surgery has been performed within 3 months before treatment; 11. Severe liver disease accompanied by decompensated cirrhosis, jaundice, ascites or hemorrhagic varices; 12. History of malignant tumors within 5 years before screening or suspected of malignant tumors during preoperative examination; 13. Patients assessed by the investigator to have comorbid diseases that may interfere with the evaluation of safety examination and efficacy; 14. Life expectancy < 6 months for any reason; 15. Pregnant or lactating women; 16. Those who cannot comply with the study protocol or any other factors that the investigator considers the subject to be potentially at risk or interfere with the subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability evaluation(phase one); | — |
Secondary
| Measure | Time frame |
|---|---|
| Painless walking time(phase one and phase two);Proportion of subjects who achieved resting pain relief and ulcer healing (if combined);Transcutaneous Oxygen Pressure (TcPO2) (phase one and phase two);putationAm Free Survival (phase one and phase two);Ankle Brachial Index (ABI)(phase one and phase two);Toe Brachial Index (TBI)(phase one and phase two); | — |
Countries
China
Contacts
Public ContactSun Aijun
Zhongshan Hospital, Fudan University
Outcome results
None listed