Stem Cell Injection to Treat Heart Damage During Open Heart Surgery

NCT01557543 | Terminated Phase 1

• 2 other identifiers: 12007812-H-0078
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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....

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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.

Interventions

Cell Therapy OTHER

Intramyocardial Injection of BMSCs

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Significant left main coronary artery stenosis (\> 50% reduction in lumen diameter).
• Left main equivalent: significant (greater than or equal to70%) stenosis of proximal LAD and proximal left circumflex artery.
• Three-vessel disease (stenosis of 50% or more in all 3 major coronary territories). (Survival benefit is greater when LVEF is
• \<0.50.)
• Two-vessel disease with significant proximal LAD stenosis and either EF \<0.50 or demonstrable ischemia on noninvasive
• testing.
• 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).
• Canadian Cardiovascular Class III or IV angina that is refractory to maximal medical therapy.
• Reversible ischemia of the left ventricular free wall and coronary artery disease corresponding to the regions of myocardial

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• NIH Heart Center at Suburban Hospital: collaborator

Study Sites (2)

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1016/s0092-8674(00)81813-9.

  PMID: 8980224 BACKGROUND

• Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald 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. doi: 10.1161/01.cir.0000043246.74879.cd.

  PMID: 12473544 BACKGROUND

• Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Schachinger 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. doi: 10.1161/01.CIR.0000095788.78169.AF. Epub 2003 Oct 13.

  PMID: 14557356 BACKGROUND

MeSH Terms

Conditions

Heart Diseases; Myocardial Ischemia; Coronary Artery Disease

Interventions

Cell- and Tissue-Based Therapy

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Pamela G Robey, Ph.D.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 16, 2012
• First Posted: March 19, 2012
• Study Start: February 29, 2012
• Primary Completion: July 25, 2017
• Study Completion: June 18, 2018
• Last Updated: July 5, 2018

Record last verified: 2018-06-18

Locations

US (2)