ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Study Overview
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Brief Summary
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Study title: A Study of Blood-Borne Autologous Angiogenic Cell Precursors Therapy in Patients with Critical Limb Ischemia ( ACPs-CLI ) Principle Investigator: Assoc.Prof. Pramook Mutirangura,M.D. Head of Division of Vascular Surgery , Department of Surgery, Faculty of Medicine Siriraj Hospital , Mahidol University, BKK,Thailand Study objective : To determine the safety and efficacy of intramuscular injection of blood-borne autologous ACPs in relieving symptoms of critical limb ischemia of patients treated with maximal medical therapy and don't have intravascular or operative revascularization option. Study Design : A pilot study , a single center, a non-randomized, open-label trial. Total expected no. of patients : 6 main selection criteria : A. Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND B. Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease: I. Ankle brachial index < 0.45 II. Toe brachial index < 0.35 III. TcPO2 / TcO2 of < 40 mmHg. C. The subject is a poor candidate for standard revascularization treatment for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy D. Age 18 to 80 years Investigational Product : At D-8 250 ml of blood drawn from the patients for production of autologous EPCs or ACPs (VescellTM). On D0 ,at least 1.5 million ACPs with viability >75 % suspended in 30 ml sterile cell culture medium will be injected 1.5 cm deep and 1.5 apart by a 23 -gauge needle into the gastrocnemius muscle of the leg chosen (ischemic leg) for treatment. For injection planning a grid of 10X10 cm will be prepared and in each point 1 ml of ACPs suspension will be injected. The study consists of 4 periods: Screening ( D-14 to-9& D-8,Treatment(D0),Acute Safety follow-up (D1&D2),Chronic follow-up (D30 & D90)period ,total follow-up of each case is 3 months. Evaluation criteria : Safety : no.& duration of adverse event & serious adverse event Efficacy :Attenuate CLI patients symptoms (Rest pain,Pain-free walking distance,Ulcer size &Gangrene dimension and intensity)

Detailed Description
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Six patients with Critical Limb Ischemia (CLI) or severe Peripheral Arterial Disease(PAD) will be enrolled, screened, treated with an injection of Blood-Borne Autologous Angiogenic Cell Precursors(ACPs) in to gastrocnemius of the ischemic leg by intramuscular under regional anesthesia. Following injection.

Official Title
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A Study of Blood-Borne Autologous Angiogenic Cells Precursors Therapy in Patients With Critical Limb Ischemia

Conditions
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Peripheral Arterial Disease, Critical Limb Ischemia

Intervention / Treatment
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* Procedure: Angiogenic Cell Precursors (ACPs) or Vescell TM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease: Ankle brachial index < 0.45 Toe brachial index < 0.35 TcPO2 / TcO2 of < 40 mmHg. The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy Age 18 to 80 years Male or non-pregnant, non-lactating female Informed consent obtained and consent form signed Exclusion Criteria: Patient having on angiography a meaningful supra popliteal occlusion that may relate to symptoms of CLI. Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment Patient who received blood transfusions during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood). Inability to communicate (that may interfere with the clinical evaluation of the patient) Major operation during the preceding 3 months Myocardial infarction or brain infarction or uncontrolled myocardial ischemia or persistent severe heart failure (EF< 25 %) during the preceding 3 months Significant valvular disease or after valve replacement during the preceding 3 months After heart transplantation Severe cardiomyopathy (EF < 25 %) Renal failure (creatinine > 2 mg/dl ) Hepatic failure Anemia (lower than 11mg/dl.hemoglobin for female and lower than 12 mg/dl for male) Abnormal coagulation tests [platelets, PT (INR), PTT] Stroke within the preceding 3 years Malignancy within the preceding 3 years Concurrent chronic or acute infectious disease Severe concurrent medical disease (e.g., septicemia, HIV-1,2/HBV/HCV infections, poorly controlled insulin-dependent diabetes mellitus ; HBA1c >8 % and proliferative retinopathy , systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis) Chronic immunomodulating or cytotoxic drugs treatment Patients who have rectal temp. above 38.40C for 2 consecutive days Patient unlikely to be available for follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Angiogenic Cell Precursors (ACPs) or Vescell TM|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | 3 months | 
| Evaluate the safety of ACPs intramuscular injection |  | 3 months | 
| Efficacy |  | 3 months | 
| Attenuate CLI patients symptoms as |  | 3 months | 
| Rest pain |  | 3 months | 
| Pain-free walking distance |  | 3 months | 
| Ulcer size |  | 3 months | 
| Gangrene dimension and intensity |  | 3 months | 
| Obtain evidence for improvement of tissue perfusion due to ACPs injection |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of CLI patients hospitalization time. |  | 3 months | 
| Decrease CLI patient amputation rate. |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells, Rest pain, claudication, chronic ischemic or non-healing ulcers, Angiogenesis, no-option cases