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

NCT ID: NCT00684060

Last Updated: 2015-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2012-02-29

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).

Detailed Description

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 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. 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. After an acute heart attack, a remodeling process is initiated in the heart in an attempt to compensate for damaged areas. Consequently, the condition of the heart muscle several weeks after a heart attack may differ considerably from the heart's condition during the acute setting. For some patients, delaying the delivery of the stem cells until 2 to 3 weeks after a heart attack may be better than initiating treatment during the acute phase. This study will evaluate the safety and effectiveness of placing adult stem cells into injured heart muscle 2 to 3 weeks after a heart attack for improving heart function in people who have had a recent heart attack and a PCI.

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 between 2 and 3 weeks 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 after 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.

Conditions

Left Ventricular Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

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

Group Type: EXPERIMENTAL

Adult stem cells

Intervention Type: BIOLOGICAL

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

2

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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

Interventions

Adult stem cells

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Adult autologous stem cells; Bone marrow mononucleated cells; Human serum albumin; HSA

Eligibility Criteria

Inclusion Criteria

1. Patients at least 21 years of age.

2. 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.

3. No contraindications to undergoing cell therapy procedure within two to three weeks following AMI and PCI.

4. Hemodynamic stability as defined as no requirement for IABP, inotropic or blood pressure supporting medications.

5. Ejection fraction following reperfusion with PCI <=45% as assessed by echocardiography.

6. Consent to protocol and agree to comply with all follow-up visits and studies.

7. 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:

1. 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).

2. 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).

3. History of any malignancy within the past five years excluding non-melanoma skin cancer or cervical cancer in-situ.

4. History of chronic anemia (hemoglobin (Hb) <9.0 mg/dl).

5. History of thrombocytosis (platelets >500k).

6. History of thrombocytopenia in the absence of recent evidence that platelet counts are normal

7. Known history of elevated INR (PT) or PTT.

8. Life expectancy less than one year.

9. History of untreated alcohol or drug abuse.

10. Currently enrolled in another Investigational drug or device trial

11. Previous CABG.

12. Previous MI resulting in LV dysfunction (LVEF <55%)

13. History of stroke or transient ischemic attack (TIA) within the past six months.

14. History of severe valvular heart disease (aortic valve area <1.0 cm2 or >3+ mitral regurgitation).

15. Pregnancy or breast feeding

16. Subjects with a known history of HIV, or has active hepatitis B, active hepatitis C, or active tuberculosis (TB)

17. Patients with active inflammatory or autoimmune disease on chronic immunosuppressive therapy.

18. Contraindications to cMRI.

19. Previous radiation to the pelvis with white blood cell count (WBC) and platelet counts below hospital specific normal values.

20. Women child bearing potential not willing to practice an active form of birth control.

21. Chronic liver disease that might interfere with survival or treatment with cell therapy.

22. Chronic renal insufficiency as defined by a creatinine ≥2.0 mg/dL or requires chronic dialysis.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Dr Lemuel A Moye III

Professor - School of Public Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Simari, MD

Role: STUDY_CHAIR

Cardiovascular Cell Therapy Research Network

Locations

University of Florida - Department of Medicine

Gainesville, Florida, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Cleveland Clinic

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Heart Institute

Houston, Texas, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 20844613 (View on PubMed)

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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 22137069 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22084195 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28490433 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27595689 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25136078 (View on PubMed)

Related Links

http://www.cctrn.org

Click here for more information on this study at the Cardiovascular Cell Therapy Research Network (CCTRN)

http://www.nhlbi.nih.gov/

Click here for the National Heart, Lung, and Blood Institute

Other Identifiers

1U01HL087318

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1 U01-HL-087318-01 (Project 2)

Identifier Type: -

Identifier Source: secondary_id

578

Identifier Type: -

Identifier Source: org_study_id