Conclusions: Local injection of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells (in the dosage and manner described) into the thigh and calf of patients with claudication does not improve peak walking disease (PWT) or magnetic resonance imaging (MRI) capillary perfusion nor were there demonstrated quality of life (QOL) improvements. In patients with completely occluded superficial femoral arteries, the number of collateral arteries did increase with ALDHbr cell injection on post hoc analysis, which suggests a potential benefit in those with more advanced disease.Summary: This National Heart Lung and Blood Institute-sponsored "Patients with Intermittent Claudication with ALDH Bright Cells" (PACE) study is a phase II randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effect of administration of ALDHbr cells vs cell-free placebo in individuals with peripheral vascular disease (PAD) and intermittent claudication. It is important to note that PACE was not designed to serve as a pivotal PAD cell therapy outcomes trial because the cell type, dosage, timing of dosing, local physiologic mechanisms, and treatment effect of potential cell types are unknown. Rather, PACE was designed as a phase II investigation that would (1) provide unbiased treatment effects for each of four primary end points, and (2) evaluate a wide set of pre hoc defined physiologic relationships that could help to direct claudication research. These secondary exploratory goals were equal in importance to the evaluation of any primary clinical end point. The change in four primary end points evaluated at 6 months were (1) peak walking time (PWT), (2) number of collateral arteries (collateral count) in the treated limb determined by magnetic resonance imaging (MRI), (3) popliteal artery peak hyperemic flow measured by MRI, and (4) MRI measurement of limb perfusion. The protocol also specified an evaluation of the relationships between MRI measures of capillary count, large artery (popliteal) flow, and capillary perfusion, with clinically relevant measurements of limb function evaluated using traditional exercise testing. Patients were aged >40 years, had claudication symptoms greater in one leg (index leg), with no inflow disease and with a significant (>50%) stenosis/occlusion of at least one infrainguinal arterial segment (any or all of superficial femoral artery, popliteal artery, or infrapopliteal arteries). Patients with prior bypass were included only if the bypass had failed and the other conditions existed. Claudication severity, patient-reported health status and QOL were evaluated by the San Diego Claudication Questionnaire (SDCQ), the Walking Impairment Questionnaire (WIQ), and Peripheral Arterial Questionnaire (PAQ). Baseline ankle-brachial index (ABI) and Gardner-Skinner exercise treadmill testing were performed. The latter documented that the index leg claudication was limited to #12 minutes. MRI angiography was performed to document anatomy and to conduct resting and postocclusi...

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