Use of Adult Autologous Stem Cells in Treating People Who Have Had a Heart Attack (The TIME Study) - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00684021

Purpose

Heart attacks are a leading cause of death for both men and women in the United States. A heart attack occurs when blood flow to the heart is restricted, commonly due to a blood clot that has formed in one of the coronary arteries. If the clot becomes large enough, blood flow to the heart can be blocked almost completely and the heart muscle in that area can suffer permanent injury or death. Although a percutaneous coronary intervention (PCI) can be used to open up the blocked artery and restore blood flow to the heart muscle, there may be a significant amount of heart tissue that has been irreversibly damaged. Recent studies have shown that adult stem cells from bone marrow may be able to improve heart function after a heart attack. This study will evaluate the safety and effectiveness of using adult stem cells for improving heart function in people who have had a recent heart attack and a PCI.

Condition	Intervention	Phase
Left Ventricular Dysfunction	Biological: Adult stem cells Biological: Placebo	Phase II

MedlinePlus related topics: Heart Attack

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Transplantation in Myocardial Infarction Evaluation (TIME) Protocol: A Phase II, Randomized, Controlled, Double-Blind Trial Evaluating the Effect of Timing on the Administration of Bone Marrow Mononuclear Cells (BMMNCs) Versus Placebo in Patients With Acute Myocardial Infarction

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Left ventricular ejection fraction (global and regional) [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Combined endpoint: first of death, reinfarction, repeat revascularization, or hospitalization for heart failure [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]
Left ventricular mass [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]
End diastolic volume [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]
End systolic volume [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]
Infarct size [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	120
Study Start Date:	July 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive active stem cell infusion 3 days after percutaneous coronary intervention (PCI).	Biological: Adult stem cells One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution
2: Active Comparator Participants will receive active stem cell infusion 7 days after PCI.	Biological: Adult stem cells One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution
3: Placebo Comparator Participants will receive placebo infusion (5% human serum albumin [HSA]) 3 days after PCI.	Biological: Placebo One time infusion of 30 ml of HSA (5%)
4: Placebo Comparator Participants will receive placebo infusion (5% HSA) 7 days after PCI.	Biological: Placebo One time infusion of 30 ml of HSA (5%)

Detailed Description:

More than 1 million Americans suffer a heart attack each year, resulting in about a 38% mortality rate. Although current treatments are able to stabilize the condition of the heart, none is able to restore heart function as it was prior to the heart attack. The permanent damage to the heart can lead to more severe problems, such as heart failure and irregular heartbeat, making the discovery of treatments to improve heart function after a heart attack important. Adult stem cells, which are immature cells that can become many different types of cells, may offer a potential means of reversing or preventing permanent damage caused by a heart attack. These specialized cells may have the ability to promote blood vessel growth, prevent cell death, and transform themselves into a number of tissues, including muscle. Recent studies have shown promise in using adult stem cells from bone marrow to reverse damage to the heart muscle caused by a heart attack, but more research is needed to assess the safety and effectiveness of stem cell use and to discover the best time to administer treatment. This study will evaluate the safety and effectiveness of placing adult stem cells into injured heart muscle for improving heart function in people who have had a recent heart attack and a PCI. Additionally, this study will help determine the best time to insert stem cells after a heart attack.

Participation in this study will last 24 months. All participants will first undergo baseline assessments that will include a medical history, a physical exam, an electrocardiogram (ECG), blood draws, an echocardiogram, and a magnetic resonance imaging (MRI) test. Participants will then be assigned randomly to receive stem cells or placebo either 3 or 7 days after their heart attack. The morning of the stem cell or placebo infusion, participants will undergo a blood draw and a bone marrow aspiration procedure of the hip bone to collect the stem cells. Later the same day, either stem cells or placebo will be infused through a catheter and into the damaged area of the heart.

For the first 24 hours following the infusion, participants will be asked to wear a small ECG machine called a Holter monitor. Participants will also be asked to record their temperature twice a day for a month after the infusion. Participants will return for follow-up visits at Months 1, 3, 6, 12, and 24 and will repeat many of the baseline assessments.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Successful PCI in the left anterior descending (LAD) artery at least 2.5 mm in diameter within 24 hours of onset of first acute anterior heart attack symptoms
No contraindications to undergoing cell therapy procedure within 3 to 7 days after acute heart attack and PCI
Hemodynamic stability, as defined as no requirement for intra-aortic balloon pump (IABP) or inotropic or blood pressure supporting medications
Ejection fraction after reperfusion with PCI less than or equal to 45%, as assessed by ECG
Woman of child bearing potential willing to use an active form of birth control

Exclusion criteria:

History of sustained ventricular arrhythmias not related to acute heart attack (evidenced by previous Holter monitoring and/or medication history for sustained ventricular arrhythmias in patient's medical chart)
Requires coronary artery bypass graft (CABG) or PCI due to the presence of residual coronary stenosis with greater than 70% luminal obstruction in the non-infarct related vessel (additional PCI of non-culprit vessels may be performed prior to enrollment)
History of any malignancy within the past 5 years excluding non-melanoma skin cancer or cervical cancer in-situ
History of chronic anemia (hemoglobin less than 9.0 mg/dL)
History of thrombocytosis (platelets greater than 500,000)
Baseline platelet count (prior to revascularization) less than 120,000 or known history of thrombocytopenia
Known history of elevated international normalized ratio (INR) prothrombin time (PT) or partial thromboplastin time (PTT)
Life expectancy less than 1 year
History of untreated alcohol or drug abuse
Currently enrolled in another investigational drug or device trial
Previous CABG
Previous heart attack resulting in left ventricular dysfunction (left ventricular ejection fraction [LVEF] less than 55%)
History of stroke or transient ischemic attack within the 6 months before study entry
History of severe valvular heart disease (aortic valve area less than 1.0 cm2 or greater than 3+ mitral regurgitation)
Pregnant or breastfeeding
Known history of HIV, hepatitis B or C infection, or testing positive for tuberculosis
Active inflammatory or autoimmune disease and receiving chronic immunosuppressive therapy
Contraindications to MRI
Previous radiation to the pelvis with white blood cell count and platelet counts below hospital specific normal values
Chronic liver disease that might interfere with survival or treatment with cell therapy
Chronic renal insufficiency, as defined by a creatinine greater than or equal to 2.0 mg/dL or requires chronic dialysis
Meets two or more of the following criteria (unless the LVEF is less than 30%):
1. Onset of symptoms to treatment PCI is less than 2 hours
2. Peak creatine kinase is less than 1500 IU/mL
3. Absence of q-wave on Day 1 EKG (post stenting)
4. Age less than 45 years

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00684021

Contacts

Contact: Shelly Sayre, MPH

713-500-9529

Shelly.L.Sayre@uth.tmc.edu

Locations

United States, Florida
University of Florida-Department of Medicine	Recruiting
Gainesville, Florida, United States, 32610
Contact: Tempa Curry 352-392-5453 Tempa.curry@medicine.ufl.edu
Contact: Eileen Handberg, PhD 352-846-0612 Handberg@medicine.ufl.edu
Principal Investigator: Carl Pepine, MD
United States, Minnesota
Minneapolis Heart Institute Foundation (Abbott Northwestern Hospital)	Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Beth Jorgenson 612-863-6289 beth.jorgenson@allina.com
Contact: Rachel Olson 612-863-3818 Rachel.Olson@allina.com
Principal Investigator: Jay Traverse, MD
United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Linda Clarke 216-445-6567 ClarkeL@ccf.org
Principal Investigator: Stephen Ellis, MD
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Judy Francescon 615-936-2735 judy.l.francescon@Vanderbilt.Edu
Contact: Kim Crum 615-936-2458 Kimberly.crum@Vanderbilt.Edu
Principal Investigator: David Zhao, MD
United States, Texas
Texas Heart Institute	Recruiting
Houston, Texas, United States, 77030
Contact: Lynette Westbrook 832-355-9405 lynette.w.westbrook@uth.tmc.edu
Contact: Deirdre Smith 832-355-9401 dxsmith@heart.thi.tmc.edu
Principal Investigator: James T. Willerson, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Robert Simari, MD

Cardiovascular Cell Therapy Research Network

More Information

Click here for more information on this study at the Cardiovascular Cell Therapy Research Network (CCTRN) This link exits the ClinicalTrials.gov site

Click here for more information on stem cells at the National Institutes of Health Stem Cell Basics This link exits the ClinicalTrials.gov site

Click here for more information about this study at the Indiana Center for Vascular Biology and Medicine This link exits the ClinicalTrials.gov site

Click here for the National Heart, Lung, and Blood Institute This link exits the ClinicalTrials.gov site

Responsible Party:	University of Texas Health Science Center Houston ( Lemuel A. Moye, MD, PhD/ Principal Investigator for the Data Coordinating Center )
Study ID Numbers:	579, 1 U01-HL-087318-01 (Project 1)
Study First Received:	May 22, 2008
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00684021
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Acute Myocardial Infarction
Global Left Ventricular Ejection Fraction
Regional Left Ventricular Ejection Fraction
Left Ventricular Mass

Infarct Size
End Systolic Volume
End Diastolic Volume

Study placed in the following topic categories:

Ventricular Dysfunction
Heart Diseases
Myocardial Ischemia
Vascular Diseases

Ventricular Dysfunction, Left
Ischemia
Infarction
Myocardial Infarction

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009