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.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed Conflict of Interest Disclosures and have reported the following: Alan T. Hirsch has 3 research grants at the University of Minnesota from Viromed, AstraZeneca, and Pluristem. He also serves as a consultant for Merck, Bayer, Anges, and Novartis. Joao A. Lima serves is funded as the MRI core lab through a grant from CAPRICOR. William R. Hiatt manages all industry funding through CPC Clinical Research, a non-profit clinical trials research center affiliate of the University of Colorado. He has grants from the following sponsors related to studies relevant to vascular disease research: AstraZeneca, Janssen, CSI, DNAVEC, Kowa, Kyushu University, Pluristem, ReNeuron, Rigel, Takeda. All remaining authors had no financial interests to disclose.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Injection template

Figure 2

Study Timeline