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: Emerson C Perin, Michael Murphy, John P Cooke, Lem Moyé, Timothy D Henry, Judy Bettencourt, Amir Gahremanpour, Nicholas Leeper, R David Anderson, William R Hiatt, Joao A Lima, Bharath Venkatesh, Shelly L Sayre, Rachel W Vojvodic, Doris A Taylor, Ray F Ebert, Alan T Hirsch, Cardiovascular Cell Therapy Research Network
• Journal: American heart journal (Am Heart J) Vol. 168 Issue 5 Pg. 667-73 (Nov 2014) ISSN: 1097-6744 [Electronic] United States
• PMID: 25440794 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Aldehyde Dehydrogenase

Topics

• Aldehyde Dehydrogenase (metabolism)
• Ankle Brachial Index
• Double-Blind Method
• Hematopoietic Stem Cell Transplantation (methods)
• Hematopoietic Stem Cells (enzymology)
• Humans
• Injections, Intramuscular
• Intermittent Claudication (etiology, therapy)
• Leg
• Magnetic Resonance Imaging
• Muscle, Skeletal (blood supply)
• Perfusion Imaging
• Peripheral Arterial Disease (complications, therapy)
• Transplantation, Autologous
• Treatment Outcome