Muscle Stimulation for Physical Function During Stem Cell Transplant
Muscle Stimulation for Physical Function During Stem Cell Transplant
Some blood, bone marrow, and lymphatic (hematologic) cancers such as Hodgkin/Non-Hodgkin
 lymphomas, chronic lymphocytic leukemia, and multiple myeloma, are over-represented in
 Veterans due to exposures including Agent Orange and an increased percentage of patients of
 African American ethnicity. Hematologic transplantation (HCT) is a common treatment for these
 cancers, but often leads to deconditioning, fatigue, muscle atrophy, and poor quality of
 life, which are associated with complications such as hospitalization and infection. Despite
 the significance of these symptoms, there are no approved treatments to prevent/reverse these
 long-term effects. The cancer itself, side effects of chemotherapy, and sedentary behavior,
 contribute to these effects. Although exercise before and after HCT has helped reduce these
 effects, it is inconsistently recommended to patients and most remain sedentary through and
 after treatment. The investigators are testing an alternative exercise strategy,
 neuromuscular electrical stimulation, to maintain physical function quality of life after
 HCT.
Hematopoietic cell transplantation (HCT) reduces physical function and muscle mass and
 increases fatigue. Neuromuscular electrical stimulation (NMES), when used as a stand-alone
 intervention, improves muscle strength and muscle mass in non-cancer patients with chronic
 obstructive pulmonary disease and chronic heart failure. The use of NMES to combat disuse
 atrophy and functional decline may be particularly useful in the HCT setting as patients
 undergo intensive preparatory chemotherapy and often experience symptoms including severe
 fatigue that leave them inactive or isolated for extended time periods surrounding the
 transplant. However, its use in the setting of cancer has not been well-established. This
 proposal will contribute to developing strategies toward optimizing the safety and outcomes
 associated with HCT in Veterans with hematologic malignancies. The overall goals of this
 study are to assess 1) the efficacy of an NMES vs Sham intervention on HCT-induced reductions
 in physical function and muscle mass and worsening of patient-reported fatigue and QOL and 2)
 the association between physical function and prolonged recovery of patient-reported fatigue
 and QOL. The investigators hypothesize that 1) NMES will attenuate the acute HCT-induced
 negative impact on physical function, body composition, QOL, and fatigue compared to Sham
 intervention, and 2) baseline physical function will be a significant predictor of 6-month
 recovery of patient-reported fatigue and QOL. Aim 1: To determine the efficacy of NMES vs.
 Sham for attenuation of HCT-induced reductions in physical function, muscle mass, and
 patient-reported QOL and fatigue in patients undergoing autologous HCT. Patients will be
 randomized 1:1 (NMES:Sham) stratified by diagnosis. Physical function, body composition, QOL,
 and fatigue will be assessed at baseline (Pre, after admission to the Bone Marrow Transplant
 Unit but before initiation of preparatory chemotherapy) and 28 plus or minus 5 days after HCT
 (Follow-up 1; FU1). The primary outcome will be between-group difference in 6MWT change at
 FU1 compared to Pre (N=23/group; 46 total). Secondary outcomes include: body composition
 measured by dual-energy x-ray absorptiometry; previously validated questionnaires (Functional
 Assessment of Chronic Illness Therapy-Fatigue; Muscle and Joint Measures) to assess
 patient-reported fatigue, QOL, symptom burden, and functional status; standard of care
 clinical/laboratory data regarding co-morbidities, adverse events, hospitalizations,
 treatment history, functional status, and clinical course; and NMES process measures such as
 feasibility, acceptability, adherence in number of sessions, accurate use,
 duration/intensity, complications, and satisfaction. Aim 2: To determine predictive ability
 of baseline 6MWT on delayed recovery of physical function, QOL, and fatigue, patient-reported
 outcomes, physical function, and chart review will be collected 6-months after HCT (FU2).
 6MWT at Pre will be used to determine significant predictors of QOL and fatigue at FU2 (N=46)
 as assessed by previously validated questionnaires. Clinical measures extracted from medical
 charts will include changes from FU1 to FU2 in standard of care clinical/laboratory data
 regarding co-morbidities, adverse events, hospitalizations, functional status, treatment
 history, disease trajectory, and survival. Aim 3 (exploratory): To investigate the acute
 impact of NMES vs. Sham during HCT on various aspects of physical function and
 patient-reported QOL for determining potential endpoints for future clinical trials.
 Exploratory measures of function (stair climbing power; muscle strength; sit-to-stand;
 handgrip strength; peak oxygen consumption) assessed at Pre and FU1 will be used to determine
 significant predictors of exploratory QOL measures (Multidimensional Fatigue Inventory; Short
 Form-36; European Organization for Research and Treatment of Cancer QOL Questionnaire)
 assessed at FU2.
Inclusion Criteria:

 -  adequate cognitive and language ability to provide consent

 -  Veteran enrolled in MTU at VAPSHCS for planned standard of care autologous HCT

 Exclusion Criteria:

 -  active deep vein thrombosis or thrombophlebitis

 -  untreated hemorrhagic disorders

 -  concomitant study inclusion in other nutritional or physical exercise interventional
 trials

 -  concomitant use of anabolic agents

 -  rhabdomyolysis or other muscle conditions where NMES is contraindicated