acps in severe pad/cli by direct intramuscular injection

Conditions: Peripheral Arterial Disease; Critical Limb Ischemia

Summary: 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)

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.

Eligibility criteria:
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

Keywords: stem cells rest pain claudication chronic ischemic or non-healing ulcers angiogenesis no-option cases