Feasibility Of Muscle Stimulation For Mitigating Cachexia During Stem Cell Transplant

PURPOSE: Hematopoietic stem cell transplant (HCT) extends survival, but often leads to cachexia: muscle atrophy, functional decline, and worsened quality of life (QOL). Traditional exercise implementation is complicated and inconsistent during HCT. We tested the feasibility of neuromuscular electrical stimulation (NMES) for mitigation of HCT-induced cachexia. METHODS: This blinded, randomized controlled trial enrolled Veterans having autologous HCT with 1:1 randomization (NMES:sham). Outcomes were assessed 4 weeks pre (PRE), 24 ± 5 days post-HCT (FU1), and 6-months post-HCT (FU2; in-progress). Outcomes: Physical function [6-minute walk test (6MWT), grip strength, max voluntary isometric contraction of knee flexors/extensors, gait speed, balance, sit-to-stand]; Body composition [fat and fat-free mass]; QOL [validated surveys]. After PRE, quadriceps, gluteals, and hamstrings were stimulated 30 mins/d, 3x/week until FU1; sham devices only delivered stimulation for 2 minutes. CK was measured every 2 weeks for safety. Intent-to-treat analysis: The primary outcome was group difference in 6MWT change. Independent t-tests compared between-groups for continuous variables or Fisher’s test for categorical variables. Data are unblinded for PRE and FU1; feasibility and safety data are presented here. RESULTS: Enrollment (n = 46) and primary outcome assessment (n = 34; attrition = 26%) are complete. There were no group differences in PRE demographics (p > 0.05), mean sessions completed (NMES: 11/17, sham: 9/16; p = 0.49), or acceptability (4/5 for each, p = 0.58). Prior to HCT, 52% of sham and 64% of NMES were < 50% adherent; 87% and 82%, respectively, were < 50% adherent after HCT. After excluding those who did not complete the primary outcome, <50% adherence rate was 31% (sham) and 39% (NMES) prior to HCT and 81% and 78%, respectively, after HCT. We observed 8 (NMES) and 4 (sham) Grade 1-2 CK elevations and three unexpected, possibly/definitely related events with NMES (all non-serious). CONCLUSIONS: NMES is safe, feasible, and acceptable during autologous HCT. Adherence was moderate before HCT and low after HCT during recovery nadir. Efficacy analyses will require adjustment for adherence and exploration of related factors like caregiver status, and PRE fitness levels between groups. Supported by: This study was funded by a Career Development Award from the US Dept. of VA (RX03245, PI: LJA). JMG receives research support from the VA (BX002807), CDMRP (PC170059), & NIH (R01CA239208, R01AG061558). LJA receives research support from the University of Washington (DK007247) & VA (RX03245).