ACPs in Severe PAD/CLI by Direct Intramuscular Injection

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

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)

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Critical Limb Ischemia
• Intervention / Treatment: Procedure: Angiogenic Cell Precursors (ACPs) or Vescell TM

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • P.O.B.4049,Ness Ziona
    • Tel viv, P.O.B.4049,Ness Ziona, Israel, 74410
      • Dr. Valentin Fulga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety	3 months
Efficacy	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
Evaluate the safety of ACPs intramuscular injection	3 months
Attenuate CLI patients symptoms as	3 months

Secondary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: August 30, 2007
• First Submitted That Met QC Criteria: August 30, 2007
• First Posted (Estimate): August 31, 2007

Study Record Updates

• Last Update Posted (Estimate): August 31, 2007
• Last Update Submitted That Met QC Criteria: August 30, 2007
• Last Verified: February 1, 2007

More Information

Terms related to this study

• Keywords: Stem cells; Angiogenesis; claudication; Rest pain; chronic ischemic or non-healing ulcers; no-option cases
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: TV-003; ACPs-CLI