Stem Cell Therapy as Adjunct to Revascularization (STAR)

Stem Cell Therapy as Adjunct to Revascularization: STAR

The purpose of this study is to determine whether it is safe to receive an injection of your own bone marrow adult stem cells (autologous BM-MNC) to your heart wall during coronary artery bypass graft (CABG).

Study Overview

• Status: Withdrawn
• Conditions: Coronary Arteriosclerosis; Coronary Artery Bypass Graft; Myocardial Revascularization
• Intervention / Treatment: Procedure: Autologous stem cell therapy; Procedure: CABG; Radiation: CMRI

Detailed Description

The experimental design will be a Phase I safety trial in which all subjects from the VA Salt Lake City Health Care System presenting with CAD and associated depressed LV function requiring myocardial surgical revascularization will be eligible for enrollment. Patients enrolled in the study will receive autologous BM-MNC as adjunct to CABG. The primary outcome measure will be safety as measured by the incidence of postoperative Serious Adverse Events (SAE) and Adverse Events (AE). The secondary outcome measures will be LV function, myocardial perfusion, and clinical improvement. The trial will have one experiment with one patient group. Group 1 (n=15) will follow standard Phase I dose escalation curve on a magnitude of 0.5 log increase after every third patient. Dose escalation will continue until a dosage of 1 x108 cells/pt is reached or maximum tolerated dose equivalent (MTDE) is identified. Cellular therapeutic products such as BM-MNCS do not possess the same pharmacologic profile as small molecule drugs, and thus, do not possess predictable metabolic activity and metabolite production, as do traditional pharmaceuticals. This can make the identity of a maximum tolerated dose somewhat difficult. We are therefore using the term MTDE instead of MTD to indicate a cell dosage that is consistent with clinical morbidity beyond obvious clinical benefit. The characteristics identifying a MTDE could be any adverse event felt to be related to the actual cell dosage or its escalation. Although unlikely, MTDE events could include microembolic phenomena, hematoma at the injection site, obvious myocardial congestion or ischemia at the injection site.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • VA Salt Lake City Health Care System, Salt Lake City

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Veteran
• Age 18 or older
• Ability to give informed consent
• Have documented CAD and depressed LV function (EF <40%) that is felt to be appropriately treated with surgical revascularization by the VA Salt Lake City Health Care System Cardiothoracic Surgery team and in accordance with the published 2004 ACC/AHA Guideline Update for Coronary Artery Bypass Graft Surgery; specifically, in accordance with the described indication for CABG in patients with Poor LV Function (see below).

Class I

1. CABG should be performed in patients with poor LV function who have significant left main coronary artery stenosis. (Level of Evidence: B)

2. CABG should be performed in patients with poor LV function who have left main equivalent:

   significant (greater than or equal to 70%) stenosis of the proximal LAD and proximal left circumflex artery. (Level of Evidence: B)

3. CABG should be performed in patients with poor LV function who have proximal LAD stenosis with 2- or 3-vessel disease. (Level of Evidence: B)

Class IIa

CABG may be performed in patients with poor LV function with significant viable noncontracting, revascularizable myocardium and without any of the above anatomic patterns. (Level of Evidence: B)

• NHYA/CCA Class I or higher
• Abnormal cardiac wall segment on preoperative data
• Acutely stable myocardium without evidence of cardiogenic shock or evolving myocardial infarction

Exclusion Criteria:

• EF 40%
• CAD not amenable to CABG
• ACC/AHA Poor LV Function Class III - CABG should not be performed in patients with poor LV function without evidence of intermittent ischemia and without evidence of significant revascularizable viable myocardium. (Level of Evidence: B) Evidence of intermittent ischemia is defined clinically by Cardiovascular Disease Classification (see chart above). Objectively, this can be demonstrated by various modalities that can demonstrate ischemic myocardium. Such modalities include SCA, Echo, CMRI, and radionucleotide imaging.
• Patients undergoing cardiac re-operation
• Patients with operable valvular disease
• Patients with preexisting malignant arrhythmia
• Patients with preexisting systemic malignancy
• Patients with a contraindication to MRI
• Presence of ongoing local or systemic infection
• Participation in another clinical trial
• Emergency operation
• Preoperative cardiogenic shock or evolving myocardial infarction
• ASA Class V or contraindication to general anesthesia
• Pregnancy
• Prisoner
• Active history of alcohol or substance abuse
• Active psychiatric history leading to potential for poor study participation and 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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; direct intramyocardial injection of cells as adjunct to CABG	Procedure: Autologous stem cell therapy; Procedure: CABG; Radiation: CMRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure will be safety as measured by the incidence of postoperative serious adverse events (SAE) and adverse events (AE).	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Ejection fraction measured by CMRI	at baseline, 3 & 6 months
Echo	at baseline, intervention, 2 weeks, 1 month, 3 months, 6 months and 1 year
Myocardial perfusion measured by gadolinium CMRI	at baseline, 3 & 6 months
Exercise tolerance testing	at baseline, 1 month, 3 months, 6 months, and 1 year

Collaborators and Investigators

• Sponsor: US Department of Veterans Affairs
• Collaborators: University of Utah
• Investigators: Study Chair: G. Russell Reiss, MD, VA Salt Lake City Health Care System, Salt Lake City

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 17, 2007
• First Submitted That Met QC Criteria: April 18, 2007
• First Posted (Estimate): April 20, 2007

Study Record Updates

• Last Update Posted (Estimate): June 11, 2014
• Last Update Submitted That Met QC Criteria: June 10, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Stem Cells; Bone Marrow Cells; Coronary Artery Bypass Graft; Cardiovascular Surgery; Phase I Study
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis
• Other Study ID Numbers: CLNB-017-04S