Cell Therapy in Patients With Chronic Ischemic Heart Disease Undergoing Cardiac Surgery

A Prospective,Randomized, Placebo-Controlled Study of Intramyocardial Injection of Autologous Bone-Marrow Mononuclear Cells in Patients With Severe, Chronic Ischemic Heart Disease Undergoing Coronary Bypass Surgery

This prospective, randomized, placebo-controlled study was designed to assess the safety, feasibility and efficacy of intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe, chronic ischemic disease scheduled to coronary artery bypass surgery.

Study Overview

• Status: Unknown
• Conditions: Left Ventricular Dysfunction; Chronic Myocardial Ischemia; Old Myocardial Infarction
• Intervention / Treatment: Procedure: bone marrow mononuclear cells injection; Procedure: placebo intramyocardial injection

Detailed Description

Severe ischemic heart disease remains a clinical challenge; many patients have undergone surgical myocardial revascularization procedures, but still remain symptomatic despite optimal medical therapy. Cell therapy with autologous bone marrow-derived cells (BMC) is a novel therapeutic strategy being tested for surgical treatment in patients with severe, chronic ischemic heart disease.

This research study is being performed to find out more information about the safety, feasibility, and efficacy of direct intramyocardial injection of autologous BMC on the myocardial perfusion and left ventricular function as an adjunctive therapy (compared to placebo) in patients undergoing coronary artery bypass surgery (CABG). The heart function evaluations will be performed by electrocardiogram, echocardiogram, and cMRI at baseline and during 6 months follow-up.

The secondary objective of this study is to assess the effect of intramyocardial injection of autologous BMC on functional class (angina/heart failure), global and cardiovascular mortality, and major adverse cardiac events after undergoing coronary artery bypass surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Changqing Gao, MD; Phone Number: +8601066938035; Email: gaochq301@yahoo.com
• Study Contact Backup: Name: Lin Zhang, MD; Phone Number: +8601066938336; Email: drzhanglin@gmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Principal Investigator: Wang Rong, MD
      • Principal Investigator: Zhang Lin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 and 75 years.
2. Scheduled to undergo CABG.
3. At least 3 months since last episode of myocardial infarction.
4. Echocardiogram-assessed LVEF between 15 and 40% (Simpson's rule).
5. Abnormal wall motion of at least one segment due to prior myocardial infarction shown by echocardiography or left ventriculography.
6. Abnormal myocardial perfusion in infarcted area by SPECT.
7. Willingness to participate and ability to provide written informed consent.

Exclusion Criteria:

1. Contraindications to magnetic resonance imaging.
2. Need for urgent or emergent revascularization.
3. Severe valvular heart disease.
4. Confirmed myocardial infarction within 14 days, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
5. Prior cardiac surgery.
6. Stroke within 3 months prior to CABG.
7. Immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
8. Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis), liver disease, (diagnosis of cirrhosis, chronic hepatitis, or elevation of serum transaminases ≥3 times the upper limit of normal), cerebrovascular disease requiring concomitant carotid endarterectomy, peripheral arterial disease (claudication as the primary factor limiting activity), active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications in the judgment of the attending cardiologist or cardiac surgeon
9. Hemoglobin less than 10g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
10. Active infection, with a temperature greater than 37.5°C within 48 hrs prior to surgery and an unexplained white blood cell count in excess of 10,000/mm3
11. Significant cognitive impairment.
12. Any condition associated with a life expectancy of less than 6 months.
13. Participation in other studies.
14. Positive laboratory test results for HIV, HBC, and HCV.
15. Pregnant woman.
16. Inability or unwillingness to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: stem cells injection; Direct intramyocardial injection of autologous bone marrow mononuclear cells during CABG	Procedure: bone marrow mononuclear cells injection; Participants will receive direct intramyocardial injection of autologous bone marrow mononuclear cells during CABG.; Other Names: autologous bone marrow mononuclear cells
Placebo Comparator: palcebo intramyocardial injection; Direct intramyocardial injection of placebo containing saline and 5% human serum albumin during CABG.	Procedure: placebo intramyocardial injection; Participants will receive between 10 and 15 placebo injections that consist of saline and 5% human serum albumin during CABG.; Other Names: palcebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major adverse cardiac events	Freedom from Major Adverse Cardiac Event: cardiac death, myocardial infarction, repeat coronary bypass grafting or percutaneous intervention of bypassed artery	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
left ventricular function	Globlal function,regional myocardial perfusion and function assessed by magnetic resonance iamge and echocardiogram	6 months

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Study Chair: Gao Changqing, MD, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): June 1, 2013

Study Registration Dates

• First Submitted: December 23, 2010
• First Submitted That Met QC Criteria: December 27, 2010
• First Posted (Estimate): December 28, 2010

Study Record Updates

• Last Update Posted (Estimate): January 12, 2011
• Last Update Submitted That Met QC Criteria: January 11, 2011
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Coronary Artery Bypass Grafting; Stem Cell Therapy; Old Myocardial Infarction
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Infarction; Infarction; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: 2006AA02A104