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Left Ventricular DysfunctionPhase 2NCT00684021

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

A Phase 2 study testing Adult stem cells in people with Left Ventricular Dysfunction, run by The University of Texas Health Science Center, Houston at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Left Ventricular Dysfunction
What is being tested?
Adult stem cells
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
5 sitesUnited States
Study dates
Jul 2008to Nov 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 23Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Florida-Department of Medicine

    Gainesville, Florida, 32610

  • Texas Heart Institute

    Houston, Texas, 77030

  • Minneapolis Heart Institute Foundation

    Minneapolis, Minnesota, 55407

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

Other trials in United States

About this 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

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.

Read the 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.

Being tested
Adult stem cells, Placebo
Keywords
Acute Myocardial Infarction, Global Left Ventricular Ejection Fraction, Regional Left Ventricular Ejection Fraction, Left Ventricular Mass, Infarct Size, End Systolic Volume, End Diastolic Volume
Medical subject headings
Ventricular Dysfunction, Left

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Adult stem cellsBiological

    Also called Adult autologous stem cells, Bone marrow mononucleated cells

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

  • PlaceboBiological

    Also called HSA

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

Study groups in NCT00684021
Study groupRoleWhat they receive
1Active comparatorParticipants will receive active adult stem cell infusion 3 days after percutaneous coronary intervention (PCI).
Receives: Biological: Adult stem cells
2Active comparatorParticipants will receive active adult stem cell infusion 7 days after PCI.
Receives: Biological: Adult stem cells
3Placebo comparatorParticipants will receive placebo infusion (5% human serum albumin [HSA]) 3 days after PCI.
Receives: Biological: Placebo
4Placebo comparatorParticipants will receive placebo infusion (5% HSA) 7 days after PCI.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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: Measured at Baseline and Month 6

  2. 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: Measured at Baseline and Month 6

  3. 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: Measured at Baseline and Month 6

Secondary outcomes (5)

  1. Clincal and Safety Outcomes

    Number of events -death, reinfarction, repeat revascularizations (target and nontarget vessels) hospitalizations for heart failure, ICD placements

    Measured: Measured from baseline to six months.

  2. Left Ventricular Mass

    Left ventricular mass (LV mass. Values reported represent the change in LV mass from baseline to six months.

    Measured: Measured at Baseline and Month 6

  3. End Diastolic Volume Index

    Left ventricular end diastolic volume index. Values reported represent the change in LV end diastolic index from baseline to six months.

    Measured: Measured at Baseline and Month 6

  4. End Systolic Volume Index

    Left ventricular end systolic volume index. Values reported represent the change in LV end systolic volume index from baseline to six months.

    Measured: Measured at Baseline and Month 6

  5. Infarct Volume

    Infarct volume(mL). Values reported represent the change in infarct volume from baseline to six months.

    Measured: Measured at Baseline and Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2008 (estimated)
  2. Study startJul 2008
  3. Primary completionMay 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00684021
Sponsor's protocol ID
579
Other IDs
U01HL087318, 1 U01-HL-087318-01 (Project 1)
Status last verified
Jun 2015
First submitted
22 May 2008
Last updated
30 Jun 2015
Data monitoring committee
Yes

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.

    PubMed 19699857

  • 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.

    PubMed 20524773

  • 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.

    PubMed 22137069

  • 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.

    PubMed 23129008

  • 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.

    PubMed 29208679

  • 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.

    PubMed 25406300

  • 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.

    PubMed 25136078

  • 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.

    PubMed 24247415

  • 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.

    PubMed 20844613

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adult stem cells in people with Left Ventricular Dysfunction, run by The University of Texas Health Science Center, Houston at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Global Left Ventricular Function (time frame: Measured at Baseline and Month 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00684021, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2015.

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