Autologous Angiogenic Cell Precursors (ACPs) for the Treatment of Peripheral Artery Disease

Critical Limb Ischemia Clinical Trial

Official title:

Autologous Stem Cell Therapy for the Treatment of Patients With Peripheral Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01584986
• Other study ID #: ACP_CLI_P01
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2012
• Last updated: April 24, 2012
• Start date: May 2008
• Est. completion date: July 2009

Study information

• Verified date: April 2012
• Source: Salus Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hungary: Scientific and Medical Research Council Ethics CommitteeHungary: Institutional Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Regeneration of the occluded peripheral arteries by autologous stem cell therapy is an emerging treatment modality for no-option patients with peripheral artery disease (PAD). The purpose of this study was to assess safety and efficacy of ex vivo expanded, peripheral blood-derived, autologous angiogenic cell precursors (ACPs) in no-option PAD patients.

Description:

Late-stage no-option PAD patients with a high risk of amputation of the affected limb were enrolled and randomized into treated and control groups. In the 10 ACP treated patients the stem cells were injected into the ischemic gastrocnemius muscle. The 10 control patients were treated with the conventional therapy. Physical examination, a treadmill walking test were performed, ankle brachial index (ABI), transcutaneous oxygen pressure (TcO2) were measured at baseline, 1 and 3 months later. Digital substraction angiography and SF-36 quality-of-life (QoL) questionnaire were also performed at baseline and 3 months later.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Subjects having 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 having one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease: I. Ankle brachial index = 0.45 or II. Toe brachial index = 0.35 or III. TcPO2 / TcO2 of = 40 mmHg.

• The subject being 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;

• After heart transplantation;

• Cardiomyopathy;

• Renal failure (creatinine > 2 mg/dl );

• Hepatic failure;

• Anemia (lower than 11 mg/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; HbAlc > 8% and proliferative retinopathy, systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis);

• Chronic immunomodulating or cytotoxic drugs treatment;

• Patients who have rectal temp. above 38.4 ºC for 2 consecutive days;

• Patient unlikely to be available for follow-up.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Peripheral Arterial Disease

Intervention

Biological:
• ACP injections
Peripheral blood-derived, ex vivo expanded autologous angiogenic cell precursors (ACPs)

Locations

Country	Name	City	State
Hungary	Kelen Hospital	Budapest
Hungary	Semmelweis University Department of Cardiovascular Surgery	Budapest

Sponsors (2)

Lead Sponsor	Collaborator
Salus Ltd.	TheraVitae Ltd.

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Evaluation the safety of ACPs intramuscular injection	3 months	Yes
Primary	Rest pain		3 months	No
Primary	Pain-free walking distance		3 months	No
Primary	Ulcer size		3 months	No
Primary	Gangrene dimension and intensity		3 months	No
Primary	Obtain evidence for improvement of tissue perfusion due to ACPs injection		3 months	No
Secondary	Reduction of CLI patients hospitalization time		3 months	No
Secondary	Decrease CLI patient amputation rate		3 months	No