ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Sponsor

TheraVitae Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT00523731

Collaborator

(none)

Enrollment

Location

13.9

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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

Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
Ankle brachial index < 0.45 II. Toe brachial index < 0.35 III. TcPO2 / TcO2 of < 40 mmHg.
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)

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease Critical Limb Ischemia	Procedure: Angiogenic Cell Precursors (ACPs) or Vescell TM	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2006

Actual Study Completion Date :

Mar 1, 2007

Outcome Measures

Primary Outcome Measures

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

Reduction of CLI patients hospitalization time. [3 months]
Decrease CLI patient amputation rate. [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr. Valentin Fulga	Tel viv	P.O.B.4049,Ness Ziona	Israel	74410

Sponsors and Collaborators

TheraVitae Ltd.

Investigators

Principal Investigator: Pramook Mutirangura, M.D., Vascular Surgery Unit,Department of Surgery,Faculty of Medicine Siriraj Hospital,Mahidol University,BKK,Thailand