Trial record 7 of 915 for:    coronary heart disease OR heart disease OR coronary artery disease OR atherosclerosis | Open Studies | NIH, U.S. Fed

Stem Cell Injection to Treat Heart Damage During Open Heart Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01557543
First received: March 16, 2012
Last updated: June 10, 2014
Last verified: November 2013
  Purpose

Background:

- Bone marrow stromal stem cells (also known as mesenchymal stem cells) have been isolated and are found to make large amounts of growth factors. Because they make growth factors, these cells can help re-grow tissue and encourage repair of damaged tissue. Tests on damaged heart muscle suggest that injecting these cells directly into damaged heart muscle can improve heart function. Researchers want to give stem cells to people who are having open heart surgery to see if they can help to repair heart muscle damage.

Objectives:

- To test the safety and effectiveness of bone marrow stromal stem cell injections given during heart surgery to treat heart muscle damage.

Eligibility:

- Individuals at least 18 years of age who are scheduled to have open heart surgery for heart artery or vein blockages.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected.
  • Participants will have bone marrow taken from both hip bones about 3 weeks before the heart surgery.
  • During the surgery, the stromal stem cells collected from the bone marrow will be given into the damaged portion of the heart muscle. The rest of the heart surgery will be performed according to standard procedures.
  • After the surgery, participants will be monitored for complications from the stromal stem cells.
  • Participants will have heart function tests to see if the stromal stem cell treatments were effective.

Condition Intervention Phase
Heart Disease
Ischemic Heart Disease
Coronary Artery Disease
Coronary Artery Disease (CAD)
Other: Cell Therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preliminary Assessment of Direct Intra-Myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for CAD With Depressed Left Ventricular Function

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells (BMSCs) in adult subjects undergoing coronary artery bypass graft (CABG) or transmyocardial revascularization (TMR).

Secondary Outcome Measures:
  • To assess if direct intra-myocardial injection of autologous BMSCs improves the patient's cardiac function, quality of life, and reduces cardiac events compared to historical controls at three and six months after intervention.

Estimated Enrollment: 24
Study Start Date: February 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Cell Therapy
    Intramyocardial Injection of BMSCs
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA
  • Consenting adult patients (male or female, aged above 18 and less than or equal to 85), and
  • Plans to undergo CABG or TMR at the NIH Heart Center at Suburban Hospital and are willing to participate.
  • Must meet indications for CABG or TMR:
  • Indications for CABG (31)

    1. Significant left main coronary artery stenosis (> 50% reduction in lumen diameter).
    2. Left main equivalent: significant (greater than or equal to70%) stenosis of proximal LAD and proximal left circumflex artery.
    3. Three-vessel disease (stenosis of 50% or more in all 3 major coronary territories). (Survival benefit is greater when LVEF is

      < 0.50.)

    4. Two-vessel disease with significant proximal LAD stenosis and either EF < 0.50 or demonstrable ischemia on noninvasive

      testing.

    5. One- or 2-vessel coronary artery disease without significant proximal LAD stenosis, but with a large area of viable

myocardium and high-risk criteria on noninvasive testing.

- Indications for TMR (32, 33).

  1. Canadian Cardiovascular Class III or IV angina that is refractory to maximal medical therapy.
  2. Reversible ischemia of the left ventricular free wall and coronary artery disease corresponding to the regions of myocardial

    ischemia.

  3. In all regions of the myocardium, the coronary disease must not be amenable to coronary artery bypass graft (CABG) or

percutaneous transluminal coronary angioplasty (PTCA), due to:

i. severe diffuse disease,

ii. lack of suitable targets for complete revascularization,

iii. lack of suitable conduits for complete revascularization

- Stable Angina. Patient?s clinical state has to be stable to receive surgical treatment. Patients must have received or currently receiving standard of care medical therapy(33) for at least 4 weeks prior to enrollment, to include:

  1. Aspirin in the absence of contraindications in patients with prior MI
  2. Beta-blockers as initial therapy in the absence of contraindications in patients with prior MI.
  3. Lipid-lowering therapy in patients with documented CAD and LDL cholesterol greater than 130 mg/dL, with a target LDL of less

    than 100 mg/dL

  4. ACE inhibitor in patients with CAD (considered significant by angiography or previous MI) who also have diabetes and/or left

ventricular systolic dysfunction.

  • Three-vessel CAD. Multi-vessel diffuse coronary artery disease not amenable to percutaneous coronary intervention.
  • LV EF less than or equal to 50% by by MRI or Echocardiogram. The left ventricle ejection fraction less than 50% evidenced the diagnosis of heart failure indicating global weakness of myocardial contractility and leaves space for functional improvement.
  • Evidence of hypokinetic segment. Regional wall motion abnormality which includes regional low/no motion, or motion in opposite direction, is a good indication for invasive intervention and can be well-compared before and after treatment.
  • Laboratory tests showed no evidence of major organ dysfunction, bleeding disorder, or infectious diseases. Patients must have organ and marrow function as defined below:

    i. Leukocytes greater than or equal to 2,500/mcL

ii. Lymphocytes greater than or equal to 800/mcL

iii. Platelets greater than or equal to 100,000/mcL

iv. Total Bilirubin less than or equal to 2mg/dL

v. AST (SGOT)/ALT (SGPT) less than or equal 1.5 times

institutional upper limit of normal (ULN)

vi. Creatinine less than or equal to institutional upper limit of

normal (ULN)

  • Must be willing to participate in 10-CC-0053 to obtain autologous bone marrow.
  • Patients must understand and sign an informed consent document that explains the nature of his/her cardiac disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, and potential risks and toxicities.

EXCLUSION CRITERIA

  • Patients who have the following conditions will be excluded from the study:
  • Acute MI. Less than three months after recent acute myocardial infarction.
  • Unstable angina. Excluded due to the propensity to deteriorate into AMI.
  • Bleeding disorder, including history of familial hemophilia, signs and symptoms of easy bruising, petechiae, or platelet count < 80,000 cells/mcL. This disorder may unnecessarily complicate the operative procedure and postoperative recovery.
  • Severe respiratory disorder, including acute asthma, chronic bronchitis, severe chronic obstructive lung disease. A disorder that would complicate the operative procedure and postoperative recovery.
  • Unable to provide informed consent on this study or on 10-CC-0053.
  • Unable to wait 3 weeks for surgery, which is the waiting period for ex-vivo cell expansion.
  • Reactive for anti-HIV, Hepatitis B surface antigen, anti-HCV or nucleic acid testing for HIV, Hepatitis B and C. An investigational component accompanying this major surgical procedure in the presence of infection has the potential to increase risk of complications, and manufacturing contaminated products risks contaminating other cellular products in CPS.
  • Pregnant or lactating females, due to the highly investigational nature of this study and its unknown effects on a developing fetus.
  • Allergic to Gentamicin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557543

Contacts
Contact: Keith A Horvath, M.D. (301) 451-7098 horvathka@mail.nih.gov
Contact: Pamela G Robey, Ph.D. (301) 496-4563 probey@dir.nidcr.nih.gov

Locations
United States, Maryland
Suburban Hospital Recruiting
Bethesda, Maryland, United States, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Pamela G Robey, Ph.D. National Institute of Dental and Craniofacial Research (NIDCR)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01557543     History of Changes
Other Study ID Numbers: 120078, 12-H-0078
Study First Received: March 16, 2012
Last Updated: June 10, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Coronary Artery Bypass Grafting
Coronary Artery Disease
Transmyocardial Revascularization
Bone Marrow Stromal Cells

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on July 28, 2014