title: 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.
abstract: Several previous studies have demonstrated that administration of autologous bone marrow-derived mononuclear cells (BMMNCs) improves cardiac function in patients after acute myocardial infarction (AMI). However, optimum timing of administration has not been investigated in a clinical trial. The Cardiovascular Cell Therapy Research Network was developed and funded by the National Heart, Lung, and Blood Institute to address important questions such as timing of cell delivery and to accelerate research in the use of cell-based therapies. The TIME trial is a randomized, phase II, double-blind, placebo-controlled clinical trial. The 5 member clinical sites of the Cardiovascular Cell Therapy Research Network will enroll 120 eligible patients with moderate-to-large anterior AMIs who have undergone successful percutaneous coronary intervention of the left anterior descending coronary artery and have a left ventricular (LV) ejection fraction </=45% by echocardiography. Participants will have bone marrow aspirations and intracoronary infusions of 150 x 10(6) BMMNCs or placebo on day 3 or day 7 post-AMI. Objectives of this study are (1) to evaluate effects of BMMNCs on regional and global LV function compared to placebo therapy in patients with acute AMI as assessed by cardiac magnetic resonance imaging at 6 months and (2) to assess whether effects of BMMNC infusion on global and regional LV function and safety are influenced by the time of administration. This study will provide further insight into the clinical feasibility and appropriate timing of autologous BMMNC therapy in high-risk patients after AMI and percutaneous coronary intervention.
authors.affiliation: Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN; University of Minnesota School of Medicine, Minneapolis, MN 55407, USA. trave004@umn.edu
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughn
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: David X M
authors.initials: DX
authors.lastname: Zhao
authors.forename: Linda B
authors.initials: LB
authors.lastname: Piller
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
authors.forename: John R
authors.initials: JR
authors.lastname: Forder
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Olson
authors.forename: Beth C
authors.initials: BC
authors.lastname: Jorgenson
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Sayre
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Vojvodic
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Skarlatos
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Moye'
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
mesh_terms: D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D016026:Bone Marrow Transplantation; D004311:Double-Blind Method; D005240:Feasibility Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D010865:Pilot Projects; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
references.citation: J Clin Invest. 2001 Jun;107(11):1395-402
references.pmid: 11390421
references.citation: Circulation. 2008 Sep 30;118(14):1425-32
references.pmid: 18794392
references.citation: Nature. 2001 Apr 5;410(6829):701-5
references.pmid: 11287958
references.citation: Nature. 2004 Apr 8;428(6983):668-73
references.pmid: 15034594
references.citation: Lancet. 2003 Aug 30;362(9385):697-703
references.pmid: 12957092
references.citation: Cytotherapy. 2008;10(2):203-11
references.pmid: 18368599
references.citation: Circulation. 2002 Nov 26;106(22):2781-6
references.pmid: 12451003
references.citation: J Cardiovasc Transl Res. 2008 Mar;1(1):64-70
references.pmid: 20559959
references.citation: Lancet. 2004 Jul 10-16;364(9429):141-8
references.pmid: 15246726
references.citation: Eur Heart J. 2007 Mar;28(6):766-72
references.pmid: 17298974
references.citation: N Engl J Med. 2006 Sep 21;355(12):1210-21
references.pmid: 16990384
references.citation: J Am Coll Cardiol. 2007 Oct 30;50(18):1761-7
references.pmid: 17964040
references.citation: Circ Res. 2004 Jun 25;94(12):1543-53
references.pmid: 15217919
references.citation: Lancet. 2006 Jan 14;367(9505):113-21
references.pmid: 16413875
references.citation: Circulation. 2004 Apr 6;109(13):1615-22
references.pmid: 15037527
references.citation: N Engl J Med. 2006 Sep 21;355(12):1199-209
references.pmid: 16990383
references.citation: Circ Res. 2004 Mar 19;94(5):678-85
references.pmid: 14739163
references.citation: Nature. 2004 Apr 8;428(6983):664-8
references.pmid: 15034593
references.citation: Am Heart J. 2006 Nov;152(5):975.e9-15
references.pmid: 17070173
references.citation: Blood. 2005 Jan 1;105(1):199-206
references.pmid: 15345590
references.citation: J Clin Invest. 2005 Feb;115(2):326-38
references.pmid: 15690083
references.citation: Nat Med. 2001 Apr;7(4):430-6
references.pmid: 11283669
references.citation: Eur Heart J. 2008 Aug;29(15):1807-18
references.pmid: 18523058