Back to resultsUse of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)
Primary Purpose
Left Ventricular Dysfunction
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Adult stem cells
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Left Ventricular Dysfunction focused on measuring Acute Myocardial Infarction, Global Left Ventricular Ejection Fraction, Regional Left Ventricular Ejection Fraction, Left Ventricular Mass, Infarct Size, End Systolic Volume, End Diastolic Volume
Eligibility Criteria
Inclusion criteria
- 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.
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 tuberculosis (TB)
- Patients with active inflammatory or autoimmune disease on chronic immunosuppressive 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.
Sites / Locations
- University of Florida - Department of Medicine
- Minneapolis Heart Institute Foundation
- Cleveland Clinic
- Vanderbilt University Medical Center
- Texas Heart Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Participants will receive active stem cell infusion 2 to 3 weeks after a percutaneous coronary intervention (PCI).
Participants will receive placebo infusion (5% human serum albumin [HSA]) 2 to 3 weeks after a PCI.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
Combined Endpoint
Combined endpoint: first of death, reinfarction, repeat revascularization, and hospitalization for heart failure. This is measured as the number of events by treatment group over the 6 month follow up period.
Left Ventricular Mass
Left ventricular mass (LV mass. Values reported represent the change in LV mass from baseline to six months.)
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.
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.
Infarct Volume
Infarct volume(mL). Values reported represent the change in infarct volume from baseline to six months.
Full Information
NCT ID
NCT00684060
First Posted
May 22, 2008
Last Updated
July 7, 2015
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00684060
Brief Title
Use of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)
Official Title
A Phase II, Randomized, Controlled, Double-Blind Pilot Trial Evaluating the Safety and Effect of Administration of Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive active stem cell infusion 2 to 3 weeks after a percutaneous coronary intervention (PCI).
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo infusion (5% human serum albumin [HSA]) 2 to 3 weeks after a PCI.
Intervention Type
Biological
Intervention Name(s)
Adult stem cells
Other Intervention Name(s)
Adult autologous stem cells, Bone marrow mononucleated cells
Intervention Description
One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution
Intervention Type
Biological
Intervention Name(s)
Placebo
Other Intervention Name(s)
Human serum albumin, HSA
Intervention Description
One time infusion of 30 ml of HSA (5%)
Primary Outcome Measure Information:
Title
Global Left Ventricular Function
Description
Left ventricular ejection fraction (global) as assessed via cardiac MRI. Values reported represent the change in Global EF from baseline to six months.
Time Frame
Measured at Baseline and Month 6
Title
Regional Left Ventricular Function (Infarct Zone Wall Motion)
Description
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.
Time Frame
Measured at Baseline and Month 6
Title
Regional Left Ventricular Function (Border Zone Wall Motion)
Description
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.
Time Frame
Measured at Baseline and Month 6
Secondary Outcome Measure Information:
Title
Combined Endpoint
Description
Combined endpoint: first of death, reinfarction, repeat revascularization, and hospitalization for heart failure. This is measured as the number of events by treatment group over the 6 month follow up period.
Time Frame
Measured at Baseline and Month 6
Title
Left Ventricular Mass
Description
Left ventricular mass (LV mass. Values reported represent the change in LV mass from baseline to six months.)
Time Frame
Measured at Baseline and Month 6
Title
End Diastolic Volume Index
Description
Left ventricular end diastolic volume index. Values reported represent the change in LV end diastolic index from baseline to six months.
Time Frame
Measured at Baseline and Month 6
Title
End Systolic Volume Index
Description
Left ventricular end systolic volume index. Values reported represent the change in LV end systolic volume index from baseline to six months.
Time Frame
Measured at Baseline and Month 6
Title
Infarct Volume
Description
Infarct volume(mL). Values reported represent the change in infarct volume from baseline to six months.
Time Frame
Measured at Baseline and Month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
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.
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 tuberculosis (TB)
Patients with active inflammatory or autoimmune disease on chronic immunosuppressive 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Simari, MD
Organizational Affiliation
Cardiovascular Cell Therapy Research Network
Official's Role
Study Chair
Facility Information:
Facility Name
University of Florida - Department of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Heart Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20844613
Citation
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.
Results Reference
background
PubMed Identifier
20524773
Citation
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.
Results Reference
background
PubMed Identifier
22137069
Citation
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.
Results Reference
background
PubMed Identifier
22084195
Citation
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.
Results Reference
result
PubMed Identifier
28490433
Citation
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.
Results Reference
derived
PubMed Identifier
27595689
Citation
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.
Results Reference
derived
PubMed Identifier
25136078
Citation
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.
Results Reference
derived
Links:
URL
http://www.cctrn.org
Description
Click here for more information on this study at the Cardiovascular Cell Therapy Research Network (CCTRN)
URL
http://www.nhlbi.nih.gov/
Description
Click here for the National Heart, Lung, and Blood Institute
Learn more about this trial
Use of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)
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