NCT00684021

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2008

Typical duration for phase_2

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 22, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 26, 2008

Completed
1 month until next milestone

Study Start

First participant enrolled

July 1, 2008

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
5 months until next milestone

Results Posted

Study results publicly available

April 4, 2013

Completed
Last Updated

June 30, 2015

Status Verified

June 1, 2015

Enrollment Period

3.8 years

First QC Date

May 22, 2008

Results QC Date

January 18, 2013

Last Update Submit

June 2, 2015

Conditions

Left Ventricular Dysfunction

Keywords

Acute Myocardial InfarctionGlobal Left Ventricular Ejection FractionRegional Left Ventricular Ejection FractionLeft Ventricular MassInfarct SizeEnd Systolic VolumeEnd Diastolic Volume

Outcome Measures

Primary Outcomes (3)

  • Global Left Ventricular Function

    Left ventricular ejection fraction (global) as assessed via cardiac MRI. Values reported represent the change in Global EF from baseline to six months.

    Measured at Baseline and Month 6

  • Regional Left Ventricular Function (Infarct Zone Wall Motion)

    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.

    Measured at Baseline and Month 6

  • Regional Left Ventricular Function (Border Zone Wall Motion)

    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.

    Measured at Baseline and Month 6

Secondary Outcomes (5)

  • Clincal and Safety Outcomes

    Measured from baseline to six months.

  • Left Ventricular Mass

    Measured at Baseline and Month 6

  • End Diastolic Volume Index

    Measured at Baseline and Month 6

  • End Systolic Volume Index

    Measured at Baseline and Month 6

  • Infarct Volume

    Measured at Baseline and Month 6

Study Arms (4)

1

ACTIVE COMPARATOR

Participants will receive active adult stem cell infusion 3 days after percutaneous coronary intervention (PCI).

Biological: Adult stem cells

2

ACTIVE COMPARATOR

Participants will receive active adult stem cell infusion 7 days after PCI.

Biological: Adult stem cells

3

PLACEBO COMPARATOR

Participants will receive placebo infusion (5% human serum albumin \[HSA\]) 3 days after PCI.

Biological: Placebo

4

PLACEBO COMPARATOR

Participants will receive placebo infusion (5% HSA) 7 days after PCI.

Biological: Placebo

Interventions

Adult stem cellsBIOLOGICAL

One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution

Also known as: Adult autologous stem cells, Bone marrow mononucleated cells
12
PlaceboBIOLOGICAL

One time infusion of 30 ml of HSA (5%)

Also known as: HSA
34

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

University of Florida-Department of Medicine

Gainesville, Florida, 32610, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

Related Publications (9)

  • 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.

    PMID: 19699857BACKGROUND

  • 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.

    PMID: 20524773BACKGROUND

  • 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.

    PMID: 22137069BACKGROUND

  • 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.

    PMID: 23129008RESULT

  • 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.

    PMID: 29208679DERIVED

  • 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.

    PMID: 25406300DERIVED

  • 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.

    PMID: 25136078DERIVED

  • 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.

    PMID: 24247415DERIVED

  • 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.

    PMID: 20844613DERIVED

Related Links

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Condition Hierarchy (Ancestors)

Ventricular DysfunctionHeart DiseasesCardiovascular Diseases

Limitations and Caveats

The choice of Day 3 or Day 7 as randomization points while based on the literature were nevertheless somewhat arbitrary. cMR-baseed ejection fractions tended to be high.

Results Point of Contact

Title
Lemuel Moye, MD, PhD
Organization
UT-Houston School of Public Health
Lemmoye@msn.com
713-500-9518

Study Officials

  • Robert Simari, MD

    Cardiovascular Cell Therapy Research Network

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor - School of Public Health

Study Record Dates

First Submitted

May 22, 2008

First Posted

May 26, 2008

Study Start

July 1, 2008

Primary Completion

May 1, 2012

Study Completion

November 1, 2012

Last Updated

June 30, 2015

Results First Posted

April 4, 2013

Record last verified: 2015-06

Locations

US(5)