Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions

NCT00365326 | Completed Phase 1

• 1 other identifier: HFM-705
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I clinical trial will evaluate the safety and efficacy of intra-coronary injection of AC133 selected autologous marrow-derived stem cells in patients with chronic coronary artery occlusion. A clinical study to determine the therapeutic potential of marrow-derived stem cells as an adjunct therapy to current standard therapies for CAD is warranted. The current initiative is to investigate a model of chronic myocardial ischemia and (1) to determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans and (2) if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging. This study is structured to evaluate the feasibility and safety of autologous AC133+ bone marrow-derived stem cell via intra-coronary injection into documented ischemic but viable myocardial zones via established collateral vessels. The epicardial vessel that normally supplies the ischemic zone must be 100% chronically occluded and considered non-revascularizable by percutaneous means.

Conditions

Coronary Occlusion

Keywords

AC133; coronary; bone marrow; autologous; coronary artery disease

Outcome Measures

Primary Outcomes (1)

• Assess the safety and feasibility of performing autologous AC133+ selected bone marrow-derived stem cell intra-coronary infusion and determine whether any benefit is achieved from the infusion of stem cells by non-invasive cardiac assessment.

  Determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans

  7days-6months

Secondary Outcomes (1)

• Improvement in ETT, reduction in ischemic area, viability improvement (nuclear stress imaging), improvement in angina (Seattle Angina Questionnaire), major adverse cardiac events assessment, echocardiogram assessment of left %EF and regional wall motion.

  7 days-6months

Study Arms (1)

Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy

EXPERIMENTAL

The Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia.

Biological: Catheter-based intracoronary injection

Interventions

Catheter-based intracoronary injection BIOLOGICAL

This Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO.

Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must have at least one region of chronically ischemic myocardium formerly perfused by a coronary artery which is now 100% occluded and not revascularizable by conventional percutaneous or surgical methods.
• Well-established collateral vessels at least 1.5-mm luminal diameter by coronary angiography to the chronically ischemic myocardium must be identified at the time of diagnostic coronary angiography.
• Evidence of viable myocardium in the area supplied by collateral conduits intended for stem cell infusion must be demonstrated by nuclear (sestamibi) stress imaging.
• Left ventricular ejection fraction of \>45% as per 2D echocardiogram.
• Patient must experience class II - IV angina as defined by the Canadian Cardiovascular Society (CCS).
• Patient will be followed by the investigating team over the 12 month follow-up period.
• The patient must be at least 18 years of age and have signed an informed consent.
• If the patient is a female of child-bearing potential, a pregnancy test is negative.

You may not qualify if:

• Patient with coronary lesions amenable to percutaneous coronary intervention including brachytherapy, or where CABG is indicated.
• Any contraindication for cardiac catheterization and percutaneous coronary intervention as per institutional guidelines.
• Any contraindication for bone marrow aspiration as per institutional guidelines.
• Myocardial infarction within the previous 3 months.
• Documented bleeding diathesis.
• Known malignancy involving the hematopoietic/lymphoid system.
• Patients with baseline ECG abnormalities that would hinder interpretation of baseline ECG uninterpretable for ischemia (e.g., left bundle branch block, left ventricular hypertrophy with strain pattern, Wolff-Parkinson-White syndrome).
• Patients with severe co-morbidities including renal failure (serum creatinine \> 2.0).
• Anticipated unavailability for follow-up visits secondary to psychological or social reasons.
• NYHA class III or IV congestive heart failure
• Anemia with hemoglobin concentration \< 8 mg/dl
• Thrombocytopenia with platelet count \< 100 x 103

Sponsors & Collaborators

• Case Western Reserve University: lead
• University Hospitals Cleveland Medical Center: collaborator
• Arteriocyte, Inc.: collaborator

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Coronary Occlusion; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Dale Adler, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Hillard Lazarus, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2006
• First Posted: August 17, 2006
• Study Start: January 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2008
• Last Updated: March 24, 2022

Record last verified: 2006-08

Locations

US (1)