ACPs in Severe PAD/CLI by Direct Intramuscular Injection

NCT00523731 | Completed Phase 1 DMC

• 2 other identifiers: TV-003ACPs-CLI
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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)

Conditions

Peripheral Arterial Disease; Critical Limb Ischemia

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (2)

• Reduction of CLI patients hospitalization time.

  3 months

• Decrease CLI patient amputation rate.

  3 months

Interventions

Angiogenic Cell Precursors (ACPs) or Vescell TM PROCEDURE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TheraVitae Ltd.: lead

Study Sites (1)

Dr. Valentin Fulga

Tel Viv, P.O.B.4049,Ness Ziona, 74410, Israel

Location

Related Publications (1)

• 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.

  PMID: 19301723 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia; Intermittent Claudication

Interventions

holo-(acyl-carrier-protein) synthase

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia; Signs and Symptoms

Study Officials

• Pramook Mutirangura, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 30, 2007
• First Posted: August 31, 2007
• Study Start: January 1, 2006
• Study Completion: March 1, 2007
• Last Updated: August 31, 2007

Record last verified: 2007-02

Locations

IL (1)