Use of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)

NCT00684060 | Completed Phase 2 Results DMC

• 3 other identifiers: 5781U01HL0873181 U01-HL-087318-01 (Project 2)
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 5

Brief Summary

More than 1 million Americans suffer heart attacks each year. 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. 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. 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 using adult stem cell infusions 2 to 3 weeks after a heart attack for improving heart function in people who have had a recent heart attack and a common procedure called a percutaneous coronary intervention (PCI).

Conditions

Left Ventricular Dysfunction

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

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)

• Combined Endpoint

  Measured at Baseline and Month 6

• 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 (2)

1

EXPERIMENTAL

Participants will receive active stem cell infusion 2 to 3 weeks after a percutaneous coronary intervention (PCI).

Biological: Adult stem cells

2

PLACEBO COMPARATOR

Participants will receive placebo infusion (5% human serum albumin \[HSA\]) 2 to 3 weeks after a PCI.

Biological: Placebo

Interventions

Adult stem cells BIOLOGICAL

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

1

Placebo BIOLOGICAL

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

Also known as: Human serum albumin, HSA

2

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients at least 21 years of age.
• Patients with first acute MI and subsequent successful primary percutaneous coronary intervention (PCI) in an artery at least 2.5 mm in diameter occurring two to three weeks before recruitment.
• No contraindications to undergoing cell therapy procedure within two to three weeks 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).

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

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 (7)

• 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: 20844613 BACKGROUND

• 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: 20524773 BACKGROUND

• 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: 22137069 BACKGROUND

• Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, Forder JR, Byrne BJ, Hatzopoulos AK, Penn MS, Perin EC, Baran KW, Chambers J, Lambert C, Raveendran G, Simon DI, Vaughan DE, Simpson LM, Gee AP, Taylor DA, Cogle CR, Thomas JD, Silva GV, Jorgenson BC, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Smith DX, Baraniuk S, Piller LB, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD; Cardiovascular Cell Therapy ResearchNetwork. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA. 2011 Nov 16;306(19):2110-9. doi: 10.1001/jama.2011.1670. Epub 2011 Nov 14.

  PMID: 22084195 RESULT

• Shahrivari M, Wise E, Resende M, Shuster JJ, Zhang J, Bolli R, Cooke JP, Hare JM, Henry TD, Khan A, Taylor DA, Traverse JH, Yang PC, Pepine CJ, Cogle CR; Cardiovascular Cell Therapy Research Network (CCTRN). Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1beta- and IL-6-Related Impairment of Bone Marrow Function. Circ Res. 2017 Jun 9;120(12):1947-1957. doi: 10.1161/CIRCRESAHA.116.309947. Epub 2017 May 10.

  PMID: 28490433 DERIVED

• Bhatnagar A, Bolli R, Johnstone BH, Traverse JH, Henry TD, Pepine CJ, Willerson JT, Perin EC, Ellis SG, Zhao DX, Yang PC, Cooke JP, Schutt RC, Trachtenberg BH, Orozco A, Resende M, Ebert RF, Sayre SL, Simari RD, Moye L, Cogle CR, Taylor DA; Cardiovascular Cell Therapy Research Network (CCTRN). Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Am Heart J. 2016 Sep;179:142-50. doi: 10.1016/j.ahj.2016.06.018. Epub 2016 Jul 6.

  PMID: 27595689 DERIVED

• 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: 25136078 DERIVED

Related Links

• Click here for more information on this study at the Cardiovascular Cell Therapy Research Network (CCTRN)
• Click here for the National Heart, Lung, and Blood Institute

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

Lack of in-vivo testing of cell product. While there are several different approaches to measure myocardial strain (myocardial tagging, DENSE, etc.), these were not employed in this study due to the need for specialized expertise at each site.

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: August 1, 2011
• Study Completion: February 1, 2012
• Last Updated: July 10, 2015
• Results First Posted: May 4, 2012

Record last verified: 2015-07

Locations

US (5)