- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00684021
Use of Adult Autologous Stem Cells in Treating People Who Have Had a Heart Attack (The TIME Study)
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida-Department of Medicine
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Minnesota
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Minneapolis, Minnesota, United States, 55407
- Minneapolis Heart Institute Foundation
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Texas
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Houston, Texas, United States, 77030
- Texas Heart Institute
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria
- Patients at least 21 years of age
- Patients with first acute MI with successful primary percutaneous coronary intervention (PCI) in an artery at least 2.5 mm in diameter within 24 hours of onset of symptoms.
- No contraindications to undergoing cell therapy procedure within three to seven days following AMI and PCI.
- Hemodynamic stability as defined as no requirement for IABP, inotropic or blood pressure supporting medications.
- Ejection fraction following reperfusion with PCI <=45% as assessed by echocardiography.
- Consent to protocol and agree to comply with all follow-up visits and studies.
- Women of child bearing potential willing to use an active form of birth control.
Exclusion criteria
Patients will be excluded from the study if they meet any of the following conditions:
- History of sustained ventricular arrhythmias not related to their AMI (evidenced by previous holter monitoring and/or medication history for sustained ventricular arrhythmias in patient's medical chart).
- Require CABG or PCI due to the presence of residual coronary stenosis >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 five years excluding non-melanoma skin cancer or cervical cancer in-situ.
- History of chronic anemia (hemoglobin (Hb) <9.0 mg/dl).
- History of thrombocytosis (platelets >500k).
- History of thrombocytopenia in the absence of recent evidence that platelet counts are normal
- Known history of elevated INR (PT) or PTT.
- Life expectancy less than one year.
- History of untreated alcohol or drug abuse.
- Currently enrolled in another investigational drug or device trial
- Previous CABG.
- Previous MI resulting in LV dysfunction (LVEF <55%)
- History of stroke or transient ischemic attack (TIA) within the past six months.
- History of severe valvular heart disease (aortic valve area <1.0 cm2 or >3+ mitral regurgitation).
- Pregnancy or breast feeding
- Subjects with a known history of HIV, or has active hepatitis B,active hepatitis C, or active TB
- Patients with active inflammatory or autoimmune disease on chronic immuno-suppressive therapy.
- Contraindications to cMRI.
- Previous radiation to the pelvis with white blood cell count (WBC) and platelet counts below hospital specific normal values.
- Women child bearing potential not willing to practice an active form of birth control.
- Chronic liver disease that might interfere with survival or treatment with cell therapy.
- Chronic renal insufficiency as defined by a creatinine ≥ 2.0 mg/dL or requires chronic dialysis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: 1
Participants will receive active adult stem cell infusion 3 days after percutaneous coronary intervention (PCI).
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One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution
Other Names:
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ACTIVE_COMPARATOR: 2
Participants will receive active adult stem cell infusion 7 days after PCI.
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One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution
Other Names:
|
PLACEBO_COMPARATOR: 3
Participants will receive placebo infusion (5% human serum albumin [HSA]) 3 days after PCI.
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One time infusion of 30 ml of HSA (5%)
Other Names:
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PLACEBO_COMPARATOR: 4
Participants will receive placebo infusion (5% HSA) 7 days after PCI.
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One time infusion of 30 ml of HSA (5%)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Global Left Ventricular Function
Time Frame: Measured at Baseline and Month 6
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Left ventricular ejection fraction (global) as assessed via cardiac MRI.
Values reported represent the change in Global EF from baseline to six months.
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Measured at Baseline and Month 6
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Regional Left Ventricular Function (Infarct Zone Wall Motion)
Time Frame: Measured at Baseline and Month 6
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One of two calculated values of regional left ventricular function as assessed via cardiac MRI.
The infarct zone is defined as the cMRI segments with the largest 2 signal intensity enhancement measures with gadolinium (using a 17-segment model).Values reported represent the change in wall motion over time in the infarct zone from baseline to six months.
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Measured at Baseline and Month 6
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Regional Left Ventricular Function (Border Zone Wall Motion)
Time Frame: Measured at Baseline and Month 6
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Two of two calculated values of regional left ventricular function assessed via cardiac MRI.
The border zone is defined as those regions adjacent to the infarct zone in which the cMRI signal intensity enhancement were in the 10%-75% range.
Values reported represent the change in wall motion over time in the border zone of the infarct from baseline to six months.
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Measured at Baseline and Month 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clincal and Safety Outcomes
Time Frame: Measured from baseline to six months.
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Number of events -death, reinfarction, repeat revascularizations (target and nontarget vessels) hospitalizations for heart failure, ICD placements
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Measured from baseline to six months.
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Left Ventricular Mass
Time Frame: Measured at Baseline and Month 6
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Left ventricular mass (LV mass.
Values reported represent the change in LV mass from baseline to six months.
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Measured at Baseline and Month 6
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End Diastolic Volume Index
Time Frame: Measured at Baseline and Month 6
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Left ventricular end diastolic volume index.
Values reported represent the change in LV end diastolic index from baseline to six months.
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Measured at Baseline and Month 6
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End Systolic Volume Index
Time Frame: Measured at Baseline and Month 6
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Left ventricular end systolic volume index.
Values reported represent the change in LV end systolic volume index from baseline to six months.
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Measured at Baseline and Month 6
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Infarct Volume
Time Frame: Measured at Baseline and Month 6
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Infarct volume(mL).
Values reported represent the change in infarct volume from baseline to six months.
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Measured at Baseline and Month 6
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Collaborators and Investigators
Publications and helpful links
General Publications
- Traverse JH, Henry TD, Vaughan DE, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, Piller LB, Penn MS, Byrne BJ, Perin EC, Gee AP, Hatzopoulos AK, McKenna DH, Forder JR, Taylor DA, Cogle CR, Olson RE, Jorgenson BC, Sayre SL, Vojvodic RW, Gordon DJ, Skarlatos SI, Moye' LA, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and design for TIME: A phase II, randomized, double-blind, placebo-controlled pilot trial evaluating the safety and effect of timing of administration of bone marrow mononuclear cells after acute myocardial infarction. Am Heart J. 2009 Sep;158(3):356-63. doi: 10.1016/j.ahj.2009.06.009. Epub 2009 Jul 23. Erratum In: Am Heart J. 2009 Dec;158(6):1045. Vaughn, Douglas E [corrected to Vaughan, Douglas E].
- Gee AP, Richman S, Durett A, McKenna D, Traverse J, Henry T, Fisk D, Pepine C, Bloom J, Willerson J, Prater K, Zhao D, Koc JR, Ellis S, Taylor D, Cogle C, Moye L, Simari R, Skarlatos S. Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience. Cytotherapy. 2010 Sep;12(5):684-91. doi: 10.3109/14653249.2010.487900.
- Zierold C, Carlson MA, Obodo UC, Wise E, Piazza VA, Meeks MW, Vojvodic RW, Baraniuk S, Henry TD, Gee AP, Ellis SG, Moye LA, Pepine CJ, Cogle CR, Taylor DA. Developing mechanistic insights into cardiovascular cell therapy: Cardiovascular Cell Therapy Research Network Biorepository Core Laboratory rationale. Am Heart J. 2011 Dec;162(6):973-80. doi: 10.1016/j.ahj.2011.05.024.
- Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DX, Ellis SG, Forder JR, Anderson RD, Hatzopoulos AK, Penn MS, Perin EC, Chambers J, Baran KW, Raveendran G, Lambert C, Lerman A, Simon DI, Vaughan DE, Lai D, Gee AP, Taylor DA, Cogle CR, Thomas JD, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Kappenman C, Westbrook L, Piller LB, Simpson LM, Baraniuk S, Loghin C, Aguilar D, Richman S, Zierold C, Spoon DB, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA. 2012 Dec 12;308(22):2380-9. doi: 10.1001/jama.2012.28726. Erratum In: JAMA. 2013 Jan 23;309(4):343. JAMA. 2015 Jul 7;314(1):86.
- Traverse JH, Henry TD, Pepine CJ, Willerson JT, Chugh A, Yang PC, Zhao DXM, Ellis SG, Forder JR, Perin EC, Penn MS, Hatzopoulos AK, Chambers JC, Baran KW, Raveendran G, Gee AP, Taylor DA, Moye L, Ebert RF, Simari RD. TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis. Circ Res. 2018 Feb 2;122(3):479-488. doi: 10.1161/CIRCRESAHA.117.311466. Epub 2017 Dec 5.
- Schutt RC, Trachtenberg BH, Cooke JP, Traverse JH, Henry TD, Pepine CJ, Willerson JT, Perin EC, Ellis SG, Zhao DX, Bhatnagar A, Johnstone BH, Lai D, Resende M, Ebert RF, Wu JC, Sayre SL, Orozco A, Zierold C, Simari RD, Moye L, Cogle CR, Taylor DA; Cardiovascular Cell Therapy Research Network (CCTRN). Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial. Circ Res. 2015 Jan 2;116(1):99-107. doi: 10.1161/CIRCRESAHA.116.304710. Epub 2014 Nov 18.
- Cogle CR, Wise E, Meacham AM, Zierold C, Traverse JH, Henry TD, Perin EC, Willerson JT, Ellis SG, Carlson M, Zhao DX, Bolli R, Cooke JP, Anwaruddin S, Bhatnagar A, da Graca Cabreira-Hansen M, Grant MB, Lai D, Moye L, Ebert RF, Olson RE, Sayre SL, Schulman IH, Bosse RC, Scott EW, Simari RD, Pepine CJ, Taylor DA; Cardiovascular Cell Therapy Research Network (CCTRN). Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes. Circ Res. 2014 Oct 24;115(10):867-74. doi: 10.1161/CIRCRESAHA.115.304353. Epub 2014 Aug 18.
- Traverse JH, Henry TD, Pepine CJ, Willerson JT, Ellis SG. One-year follow-up of intracoronary stem cell delivery on left ventricular function following ST-elevation myocardial infarction. JAMA. 2014 Jan 15;311(3):301-2. doi: 10.1001/jama.2013.282674. No abstract available. Erratum In: JAMA. 2015 Jul 7;314(1):86.
- Traverse JH, Henry TD, Vaughan DE, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, Simpson LM, Penn MS, Byrne BJ, Perin EC, Gee AP, Hatzopoulos AK, McKenna DH, Forder JR, Taylor DA, Cogle CR, Baraniuk S, Olson RE, Jorgenson BC, Sayre SL, Vojvodic RW, Gordon DJ, Skarlatos SI, Moye LA, Simari RD; Cardiovascular Cell Therapy Research Network. LateTIME: a phase-II, randomized, double-blinded, placebo-controlled, pilot trial evaluating the safety and effect of administration of bone marrow mononuclear cells 2 to 3 weeks after acute myocardial infarction. Tex Heart Inst J. 2010;37(4):412-20.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 579
- U01HL087318 (NIH)
- 1 U01-HL-087318-01 (Project 1)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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