Stem Cell Heart Injections During Laser Revascularization Surgery for Treatment of Chronic Ischemic Heart Disease

Prospective Controlled Trial of Intra-Myocardial Infusion of Bone Marrow Derived Autologous CD133+ Selected Cells During Trans-Myocardial Laser Revascularization (TMR) in Patients With Chronic Ischemic Heart Disease

Assess the safety and effectiveness of stem cell application with regard to improvement in regional myocardial function in patients receiving Trans-Myocardial Laser Revascularization (TMR) and stem cells.

Study Overview

• Status: Completed
• Conditions: Chronic Ischemic Heart Disease
• Intervention / Treatment: Drug: Bone Marrow Derived Autologous CD133+ Selected Cell Product

Detailed Description

Multiple case experiences and studies have been published reviewing clinical experiences with Carbon Dioxide Trans-Myocardial Laser Revascularization (TMR) and autologous bone marrow derived cell application. These experiences have demonstrated perfusion improvements, ejection fraction improvements and improvements in angina or heart failure symptoms. The investigators elected to examine the use of CD133 positive (CD133+) BM-derived stem cells because of their pluripotent nature and the fact that during the CD133 selection process inflammatory cells present in the bone marrow are being discarded. CD133+ is a recently discovered marker for more primitive bone marrow derived multipotent stem and endothelial progenitor cells and is of particular interest in studies directed to therapeutic angiogenesis, as these cells have been shown to differentiate into endothelial and myogenic cell lines. Multiple studies have utilized BM derived cells for myocardial regeneration. Patients who received CD133+ cells showed improved perfusion at injection sites of stem cells leading to a significant increase in volume of left ventricular ejection fraction, regional wall motion in the infarct zone, and a reduction in end systolic left ventricular volume.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky HealthCare

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:

• Presence of at least two vessel coronary artery disease not amenable to direct revascularization
• Area of interest defined as part of free left ventricular vall with reduced contractility
• Demonstration of reduced perfusion in the area of interest (>30% of free wall)
• Global ejection fraction 30-45% with symptoms class >_ II on the NYHA scale
• Significant refractory angina defined as symptoms class >_ III that are refractory to maximal medical and anti-angina therapy
• Expected survival of at least two years

Exclusion Criteria:

• Any condition that prevents successful stem cell collection or application, e.g. systemic infection, puncture for stem cell collection impossible
• Any condition that may adversely affect bone marrow such as malignancy or prior irradiation to the pelvic bone
• Mitral valve insufficiency > moderate grade
• History of ventricular arrhythmias not controlled by medication and/or AICD
• Need for additional heart surgery (i.e. valve replacement)
• Emergency or salvage operation defined as within 48 hours of diagnosis
• Evidence of left ventricular thrombus
• Previous heart surgery within the last 6 months
• Increased Troponin T (> 3X ULN) in patients with unstable angina at time of intervention
• History of symptomatic carotid disease within the last 3 months prior to study intervention
• Ejection fraction < 30%
• End stage renal disease
• Untreatable cancer, current or within preceding 5 years
• Severe COPD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Phase I Open Label; open label bone marrow derived autologous CD133+ selected stem cell application in patients receiving trans-myocardial laser revascularization to improve regional myocardial function as detailed below: Drug: CD133+ selected stem cells Dosage: Single injection of 0.1-0.2 ml around each laser channel Frequency: 10-20 channels Duration: Trans-Myocardial Revascularization

Drug: Bone Marrow Derived Autologous CD133+ Selected Cell Product; Injection of bone marrow derived autologous CD133+ cell product into laser channels during Trans-Myocardial Revascularization; Other Names: Stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Treatment-emergent serious adverse events (SAE) and adverse events	Major adverse cardiac event and adverse events defined in the common toxicity criteria	Assess from Procedure through 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular ejection fraction compared to baseline	Measured as a percentage by Echocardiography	Assessed at baseline, 6 months, and 12 months
Change in myocardial regional function compared to baseline	Measured by nuclear scanning.	Assessed at baseline and 6 months
Change in myocardial regional viability compared to baseline	Measured by nuclear scanning.	Assessed at baseline and 6 months
Change in distance walked compared to baseline	Measured in feet during a 6 minute walk test	Assessed at baseline, 3 months, 6 months, and 12 months
Change in quality of life associated with heart failure compared to baseline	Measured using the Kansas City Cardiomyopathy Questionnaire.	Assessed at baseline, 3 months, 6 months, and 12 months
Change in class of angina compared to baseline	Measured using the Canadian Cardiovascular Society Grading Scale.	Assessed at baseline, 3 months, 6 months, and 12 months.
Change in class of heart failure compared to baseline	Measured using the New York Heart Association Questionnaire	Assessed at baseline, 3 months, 6 months, and 12 months.
Change in regional left ventricular wall motion compared to baseline	Measured using echocardiogram.	Assessed at baseline, 6 months, and 12 months
Change in quality of life associated with angina compared to baseline	Measured using the Seattle Angina Questionnaire	Assessed at baseline, 3 months, 6 months, and 12 months

Collaborators and Investigators

• Sponsor: Michael Sekela
• Investigators: Principal Investigator: Michael Sekela, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2016
• Primary Completion (Actual): November 12, 2020
• Study Completion (Actual): November 12, 2020

Study Registration Dates

• First Submitted: June 17, 2016
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: 15-1051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: to be determined per principal investigator and statistician