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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-H-0078

Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 85

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Coronary Artery Bypass Grafting;
Coronary Artery Disease;
Transmyocardial Revascularization;
Bone Marrow Stromal Cells

Recruitment Keyword(s)

None

Condition(s)

Heart Disease;
Ischemic Heart Disease;
Coronary Artery Disease;
Coronary Artery Disease (CAD)

Investigational Drug(s)

Autologous Bone Marrow Stromal Cells

Investigational Device(s)

None

Intervention(s)

Other: Cell Therapy

Supporting Site

National Heart, Lung and Blood InstituteNIH Heart Center at Suburban Hospital

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.

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Eligibility

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)

a. Significant left main coronary artery stenosis (> 50% reduction in lumen diameter).

b. Left main equivalent: significant (greater than or equal to70%) stenosis of proximal LAD and proximal left circumflex artery.

c. Three-vessel disease (stenosis of 50% or more in all 3 major coronary territories). (Survival benefit is greater when LVEF is

< 0.50.)

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

testing.

e. 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).

a. Canadian Cardiovascular Class III or IV angina that is refractory to maximal medical therapy.

b. Reversible ischemia of the left ventricular free wall and coronary artery disease corresponding to the regions of myocardial

ischemia.

c. 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:

a. Aspirin in the absence of contraindications in patients with prior MI

b. Beta-blockers as initial therapy in the absence of contraindications in patients with prior MI.

c. 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

d. 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.


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Citations:

Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996 Dec 27;87(7):1171-80.

Assmus B, Sch(SqrRoot) chinger V, Teupe C, Britten M, Lehmann R, D(SqrRoot)(Delta)bert N, Gr(SqrRoot) nwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002 Dec 10;106(24):3009-17.

Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Sch(SqrRoot) chinger V, Dimmeler S, Zeiher AM. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation. 2003 Nov 4; 108(18):2212-8. Epub 2003 Oct 13.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Pamela G. Robey, Ph.D.
National Institute of Dental And Craniofacial Research (NIDCR)
National Institutes of Health
Building 30
Room 228
30 Convent Drive
Bethesda, Maryland 20892
(301) 496-4563
probey@dir.nidcr.nih.gov

Keith A. Horvath, M.D.
National Institute of Dental And Craniofacial Research (NIDCR)
BG 10 RM B1D47
10 CENTER DR
BETHESDA MD 20814
(301) 451-7098
horvathka@mail.nih.gov

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT01557543

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