title: Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells.
abstract: Peripheral artery disease (PAD) is recognized as a public health issue because of its prevalence, functional limitations, and increased risk of systemic ischemic events. Current treatments for claudication, the primary symptom in patients with PAD, have limitations. Cells identified using cytosolic enzyme aldehyde dehydrogenase (ALDH) may benefit patients with severe PAD but has not been studied in patients with claudication. PACE is a randomized, double-blind, placebo-controlled clinical trial conducted by the Cardiovascular Cell Therapy Research Network to assess the safety and efficacy of autologous bone marrow-derived ALDH(br) cells delivered by direct intramuscular injections in 80 patients with symptom-limiting intermittent claudication. Eligible patients will have a significant stenosis or occlusion of infrainguinal arteries and a resting ankle-brachial index less than 0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary end points are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance imaging at 6 months compared with baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging-based end points that may help to quantify the biologic and mechanistic effects of cell therapy. This trial will collect important mechanistic and clinical information on the safety and efficacy of ALDH(br) cells in patients with claudication and provide valuable insight into the utility of advanced magnetic resonance imaging end points.
authors.affiliation: Texas Heart Institute, Houston, TX.
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Michael
authors.initials: M
authors.lastname: Murphy
authors.affiliation: Houston Methodist Research Institute, Houston, TX.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.affiliation: The University of Texas Health Science Center School of Public Health, Houston, TX. Electronic address: lemmoye@msn.com.
authors.forename: Lem
authors.initials: L
authors.lastname: Moyé
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: The University of Texas Health Science Center School of Public Health, Houston, TX.
authors.forename: Judy
authors.initials: J
authors.lastname: Bettencourt
authors.affiliation: Texas Heart Institute, Houston, TX.
authors.forename: Amir
authors.initials: A
authors.lastname: Gahremanpour
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Leeper
authors.affiliation: University of Florida School of Medicine, Gainesville, FL.
authors.forename: R David
authors.initials: RD
authors.lastname: Anderson
authors.affiliation: University of Colorado School of Medicine, Denver, CO.
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Joao A
authors.initials: JA
authors.lastname: Lima
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Bharath
authors.initials: B
authors.lastname: Venkatesh
authors.affiliation: The University of Texas Health Science Center School of Public Health, Houston, TX.
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Sayre
authors.affiliation: The University of Texas Health Science Center School of Public Health, Houston, TX.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Vojvodic
authors.affiliation: Texas Heart Institute, Houston, TX.
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, MD.
authors.forename: Ray F
authors.initials: RF
authors.lastname: Ebert
authors.affiliation: Lillehei Heart Institute, Cardiovascular Division, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Hirsch
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D055109:Ankle Brachial Index; D004311:Double-Blind Method; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D007273:Injections, Intramuscular; D007383:Intermittent Claudication / Q000209:etiology / Q000628:therapy*; D007866:Leg; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000098:blood supply*; D055420:Perfusion Imaging; D058729:Peripheral Arterial Disease / Q000150:complications / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000444:Aldehyde Dehydrogenase