ACPs in Severe PAD/CLI by Direct Intramuscular Injection

NCT ID: NCT00523731

Last Updated: 2007-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2007-03-31

Brief 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)

Detailed Description

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.

Conditions

Peripheral Arterial Disease; Critical Limb Ischemia

Keywords

Stem cells; Rest pain; claudication; chronic ischemic or non-healing ulcers; Angiogenesis; no-option cases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Angiogenic Cell Precursors (ACPs) or Vescell TM

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TheraVitae Ltd.

INDUSTRY

Sponsor Role: lead

Principal Investigators

Pramook Mutirangura, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vascular Surgery Unit,Department of Surgery,Faculty of Medicine Siriraj Hospital,Mahidol University,BKK,Thailand

Locations

Dr. Valentin Fulga

Tel Viv, P.O.B.4049,Ness Ziona, Israel

Countries

Israel

References

Mutirangura P, Ruangsetakit C, Wongwanit C, Chinsakchai K, Porat Y, Belleli A, Czeiger D. Enhancing limb salvage by non-mobilized peripheral blood angiogenic cell precursors therapy in patients with critical limb ischemia. J Med Assoc Thai. 2009 Mar;92(3):320-7.

Reference Type: DERIVED

PMID: 19301723 (View on PubMed)

Other Identifiers

ACPs-CLI

Identifier Type: -

Identifier Source: secondary_id

TV-003

Identifier Type: -

Identifier Source: org_study_id