The Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart Failure Trial (TAC-HFT) - Full Text View

Sponsor:	University of Miami
Collaborator:	The EMMES Corporation
Information provided by (Responsible Party):	Joshua M Hare, University of Miami
ClinicalTrials.gov Identifier:	NCT00768066

Purpose

The technique of transplanting progenitor cells into a region of damaged myocardium, termed cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be readily available, easy to culture to ensure adequate quantities for transplantation, and able to survive in host myocardium; often a hostile environment of limited blood supply and immunorejection. Whether effective cellular regenerative strategies require that administered cells differentiate into adult cardiomyocytes and couple electromechanically with the surrounding myocardium is increasingly controversial, and recent evidence suggests that this may not be required for effective cardiac repair. Most importantly, transplantation of graft cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a number of candidate cells have been transplanted in experimental models, including fetal and neonatal cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac precursors residing within the heart itself. There has been substantial clinical development in the use of whole bone marrow and skeletal myoblast preparations in studies enrolling both post-infarction patients, and patients with chronic ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived mesenchymal stem cells (MSCs) have also been studies clinically.

Currently, bone marrow or bone marrow-derived cells represent highly promising modality for cardiac repair. The totality of evidence from trials investigating autologous whole bone marrow infusions into patients following myocardial infarction supports the safety of this approach. In terms of efficacy, increases in ejection fraction are reported in the majority of the trials.

Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and problematic condition; definitive therapy in the form of heart transplantation is available to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for acute MI, but represents a potentially important alternative for this disease.

Condition	Intervention	Phase
Stem Cell Transplantation Ventricular Dysfunction, Left	Biological: Autologous human mesenchymal cells (hMSCs) Biological: Autologous human bone marrow cells (hBMCs) Biological: Placebo	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Bone Marrow or Mesenchymal) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Heart Failure

U.S. FDA Resources

Further study details as provided by University of Miami:

Primary Outcome Measures:

Incidence of TE-SAE define as composite of death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, ventricular arrhythmias >15 sec. or with hemodynamic compromise or atrial fibrillation [ Time Frame: one month post-catheterization ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

MRI and echocardiographic-derived measures of left ventricular function: -- Difference between the baseline, 6-month, and 18-month infarct scar size (ISS)as determined by delayed contrast-enhanced MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-catheterization ] [ Designated as safety issue: No ]
MRI and echocardiographic-derived measures of left ventricular function: -- Difference between regional left ventricular function (region of MSC injection) as determined by MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-catheterization ] [ Designated as safety issue: No ]
MRI and echocardiographic-derived measures of left ventricular function: -- Difference between regional left ventricular wall thickening as determined by MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-catheterization ] [ Designated as safety issue: No ]
MRI and echocardiographic-derived measures of left ventricular function: -- Difference between left ventricular end diastolic wall thickness as determined by MRI and echocardiogram. [ Time Frame: Baseline and Month 6 and Month 12 post-catheterization ] [ Designated as safety issue: No ]
MRI and echocardiographic-derived measures of left ventricular function: -- Difference between left ventricular ejection fraction, and end diastolic and end systolic volumes, as determined by MRI and echocardiogram. [ Time Frame: Baseline and Month 6 and Month 12 post-catheterization ] [ Designated as safety issue: No ]
MRI and echocardiographic-derived measures of left ventricular function: -- Difference between the baseline, 6-month, and 18-month left ventricular regional myocardial perfusion as determined by MRI. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Peak VO2 (by treadmill determination). [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Six-minute walk test. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
NYHA functional class. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Minnesota Living with Heart Failure (MLHF) questionnaire. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Incidence of the Major Adverse Cardiac Events (MACE) endpoint, defined as the composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent MI. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: Yes ]
Ectopic tissue formation. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: Yes ]
48-hour ambulatory ECG recordings. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Hematology, clinical chemistry and urinalysis values. [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Pulmonary function (measured by the forced expiratory volume in 1 second [FEV1]). [ Time Frame: During 6 month follow-up period post-catheterization and at 12 months post-catheterization ] [ Designated as safety issue: No ]
Serial troponin and CK-MB values (every 12 hours for the first 48 hours post CABG). [ Time Frame: Measured every 12 hours for the first 48 hours post-catheterization ] [ Designated as safety issue: Yes ]
Post-cardiac catheterization echocardiogram. [ Time Frame: Day 1 post-catheterization ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	August 2008
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive an injection of 100 million or 200 million autologous human mesenchymal stem cells (hMSCs).	Biological: Autologous human mesenchymal cells (hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.25 mL per injection for a total of 1 x 108 (100 million) hMSCs x 10 injections or a dose of 0.5 mL per injection for a total of 2 x 108 (200 million) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
Experimental: 2 Participants will receive an injection of 100 million or 200 million autologous human bone marrow cells (hBMCs).	Biological: Autologous human bone marrow cells (hBMCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.25 mL per injection for a total of 1 x 108 (100 million) hBMCs x 10 injections or a dose of 0.5 mL per injection for a total of 2 x 108 (200 million) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
Placebo Comparator: 3 Participants will receive a placebo injection of phosphate-buffered saline (PBS) and 1% human serum albumin (HAS).	Biological: Placebo Participants will receive 0.5 mL injections of phosphate-buffered saline (PBS) and 1% human serum albumin (HAS) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.

Eligibility

Ages Eligible for Study:	21 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI.
Be a candidate for cardiac catheterization.
Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction.
Ejection fraction less than or equal to 50%.
Able to perform a metabolic stress test.

Exclusion Criteria:

Baseline glomerular filtration rate < 45 ml/min/1.73m2.
Presence of a mechanical aortic valve or heart constrictive device.
Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to an orifice area of 1.5cm2 or less).
Documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete heart block) or QTc interval > 550 ms on screening ECG. In addition; patients with sustained or a short run of ventricular tachycardia on ECG or 48 hour Ambulatory ECG during the screening period will be removed from the protocol.
Documented unstable angina.
AICD firing in the past 60 days prior to the procedure.
Contra-indication to performance of a magnetic resonance imaging scan.
Be eligible for or require coronary artery revascularization.
Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation.
Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three times the ULN.
Have a coagulopathy condition = (INR > 1.3) not due to a reversible cause.
Known, serious radiographic contrast allergy.
Known allergies to penicillin or streptomycin.
Organ transplant recipient.
Clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
Non-cardiac condition that limits lifespan to < 1 year.
On chronic therapy with immunosuppressant medication.
Serum positive for HIV, hepatitis BsAg, or non-viremic hepatitis C.
Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768066

Contacts

Contact: Joshua M Hare, MD	305-243-5579	jhare@med.miami.edu
Contact: Darcy L Velazquez, RN,BSN	305-243-9106	dvelazqu@med.miami.edu

Locations

United States, Florida
University of Miami Miller School of Medicine	Recruiting
Miami, Florida, United States, 33136
Contact: Joshua M Hare, MD 305-243-5579 jhare@med.miami.edu
Principal Investigator: Joshua M Hare, MD

Sponsors and Collaborators

University of Miami

The EMMES Corporation

Investigators

Principal Investigator:	Joshua M Hare, MD	University of Miami, Miller School of Medicine
Principal Investigator:	Alan W Heldman, MD	University of Miami, Miller School of Medicine
Principal Investigator:	Juan P Zambrano, MD	University of Miami, Miller School of Medicine
Study Director:	Richard P Schwarz, PhD	CV Ventures

More Information

No publications provided by University of Miami

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Trachtenberg B, Velazquez DL, Williams AR, McNiece I, Fishman J, Nguyen K, Rouy D, Altman P, Schwarz R, Mendizabal A, Oskouei B, Byrnes J, Soto V, Tracy M, Zambrano JP, Heldman AW, Hare JM. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J. 2011 Mar;161(3):487-93.

Responsible Party:	Joshua M Hare, Director, Interdisciplinary Stem Cell Institute, University of Miami
ClinicalTrials.gov Identifier:	NCT00768066 History of Changes
Other Study ID Numbers:	TAC-HFT-07-001
Study First Received:	October 3, 2008
Last Updated:	February 2, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:

Chronic Ischemic Left Ventricular Dysfunction

Additional relevant MeSH terms:

Heart Failure
Myocardial Infarction
Ventricular Dysfunction, Left
Ventricular Dysfunction

Heart Diseases
Cardiovascular Diseases
Myocardial Ischemia
Vascular Diseases

ClinicalTrials.gov processed this record on May 23, 2012