Back to results

ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Primary Purpose

Peripheral Arterial Disease, Critical Limb Ischemia

Status

Completed

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

Angiogenic Cell Precursors (ACPs) or Vescell TM

About this trial

This is an interventional treatment trial for Peripheral Arterial Disease focused on measuring Stem cells, Rest pain, claudication, chronic ischemic or non-healing ulcers, Angiogenesis, no-option cases

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Dr. Valentin Fulga

Outcomes

Primary Outcome Measures

Safety

Evaluate the safety of ACPs intramuscular injection

Efficacy

Attenuate CLI patients symptoms as

Rest pain

Pain-free walking distance

Ulcer size

Gangrene dimension and intensity

Obtain evidence for improvement of tissue perfusion due to ACPs injection

Secondary Outcome Measures

Reduction of CLI patients hospitalization time.

Decrease CLI patient amputation rate.

Full Information

NCT ID

NCT00523731

First Posted

August 30, 2007

Last Updated

August 30, 2007

Sponsor

TheraVitae Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00523731

Brief Title

ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2007

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

March 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

TheraVitae Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Arterial Disease, Critical Limb Ischemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Procedure

Intervention Name(s)

Angiogenic Cell Precursors (ACPs) or Vescell TM

Primary Outcome Measure Information:

Title

Safety

Time Frame

3 months

Title

Evaluate the safety of ACPs intramuscular injection

Time Frame

3 months

Title

Efficacy

Time Frame

3 months

Title

Attenuate CLI patients symptoms as

Time Frame

3 months

Title

Rest pain

Time Frame

3 months

Title

Pain-free walking distance

Time Frame

3 months

Title

Ulcer size

Time Frame

3 months

Title

Gangrene dimension and intensity

Time Frame

3 months

Title

Obtain evidence for improvement of tissue perfusion due to ACPs injection

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Reduction of CLI patients hospitalization time.

Time Frame

3 months

Title

Decrease CLI patient amputation rate.

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pramook Mutirangura, M.D.

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dr. Valentin Fulga

City

Tel viv

State/Province

P.O.B.4049,Ness Ziona

ZIP/Postal Code

74410

Country

Israel

12. IPD Sharing Statement

Citations:

PubMed Identifier

19301723

Citation

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.

Results Reference

derived

Learn more about this trial

ACPs in Severe PAD/CLI by Direct Intramuscular Injection

We'll reach out to this number within 24 hrs