Abstract 4934: CLI-Bright: A Phase I Randomized Blinded Clinical Trial Comparing the Effect of Intramuscular Injection of Autologous Bone Marrow Derived Aldehyde Dehydrogenase Bright Cells and Mononuclear Stem Cells in Patients With Critical Limb Ischemia
Background: Critical limb ischemia (CLI) is an advanced stage of peripheral arterial disease (PAD) associated with high morbidity and mortality. Functional improvement and lower amputation rates have been reported in clinical studies using intramuscular (IM) injection of autologous bone marrow mononuclear cells (ABMMNC) into ischemic limbs. Aldehyde Dehydrogenase-Bright (ALDHbr) cells are a highly potent subpopulation of ABMMNC and preclinical studies suggest that ALDHbr cells may contribute more effectively to angiogenesis. Therefore, we investigated the safety and efficacy of ALDHbr compared to ABMMNC in CLI patients who were not candidate for revascularization.
Methods: 21 patients (mean age 72, 13 men) with ankle-brachial index (ABI) < 0.5 and Rutherford category (RC) 4 – 5, were randomized to receive 10 IM injections of either ALDHbr cells (n=11) or ABMMNCs (n=10) into the gastrocnemius muscle of the affected limb. Primary outcomes at 3 months were safety and efficacy based on ABI, transcutaneous partial pressure of oxygen (tcPO2), RC, and ischemic ulcer grade. Paired t-test or Wilcoxon sign test was used for statistical analysis.
Results: The mean number of ALDHbr cells and ABMMNCs implanted were 1.33 × 106 and 1.207 × 106. There were no significant clinical differences between the two groups at baseline. There was no adverse reaction to IM injections. One amputation occurred in each group. One death occurred in ALDHbr patients, which was not related to the therapy. At 3 months in ALDHbr group, ABI and RC improved 0.14 (p=0.025) and 0.64 (p=0.04), respectively. In the ABMMNC group, there were non significant changes in ABI and RC (0.08 and 0.67, respectively). No significant changes from baseline were noted in tcPO2 and ischemic ulcer grade in either group.
Conclusion: IM implantation of ALDHbr cells appears to be safe and our efficacy measures will be the first to compare selected from unselected cells in treatment of critical limb ischemia.