Muscle Stimulation for Physical Function During Stem Cell Transplant

Neuromuscular Electrical Stimulation for Physical Function Maintenance During Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Completed
• Conditions: Autologous Hematopoietic Stem Cell Transplant
• Intervention / Treatment: Device: RS-4i Plus Sequential Stimulator (RS Medical, Vancouver, WA)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98108-1532
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• implanted cardiac device
• baseline patient-reported muscle soreness of 5-6 on the soreness likert scale that is unrelated to recent physical exertion
• history of prior hematologic stem cell transplant
• probable or definitive liver cirrhosis
• reduced renal clearance defined as Stage 4 chronic kidney disease (glomerular filtration rate <45 ml/min/1.73 m2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active NMES; asymmetric biphasic waveforms at 71 pulses per second frequency (Hz), 400 s pulse duration, 5:10s on:off time (50% duty cycle), and 1.5s ramp-up time. Participants will be in control of the muscle stimulator devices at all times and will be instructed to perform all sessions in the supine position. Bilateral NMES will be delivered via asymmetric, biphasic using four cutaneous parallel channels delivered simultaneously using 2"x4" or 3"x5" self-adhesive electrodes. For the active NMES group, participants will be encouraged to increase the amplitude to a level of moderate discomfort, such as that experienced during conventional exercise, but not to induce pain. At minimum, the amplitude should induce visible muscle contraction.	Device: RS-4i Plus Sequential Stimulator (RS Medical, Vancouver, WA); Active or Sham Neuromuscular electrical stimulation. US Food and Drug Administration-approved 2012; Other Names: NMES, e-stim
Sham Comparator: Sham NMES; The amplitude of the muscle stimulators for the Sham group will be capped at 15 milliamperes so patients will only feel cutaneous sensation without achieving muscle contraction.	Device: RS-4i Plus Sequential Stimulator (RS Medical, Vancouver, WA); Active or Sham Neuromuscular electrical stimulation. US Food and Drug Administration-approved 2012; Other Names: NMES, e-stim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Minute Walk Test	Manual and mobile application assessment	change from before to 1month after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported Fatigue	Anderson Symptom Assessment Scale (range 0-10 where 10 is maximum fatigue)	change from before to 1month after transplant
Lean Body Mass	dual energy fan-beam x-ray absorptiometry; bioelectrical impedance	change from before to 1month after transplant
Physical Activity	triaxial accelerometry	change from before to 1month after transplant
NMES adherence	Number of sessions completed out of total sessions	1month after transplant
Muscle Damage (safety)	plasma creatine kinase	change from before to 2 weeks after intervention initiation
Muscle Damage (safety)	plasma creatine kinase	change from before to 4 weeks after intervention initiation
Muscle Damage (safety)	plasma creatine kinase	change from before to 6 weeks after intervention initiation
Muscle Damage (safety)	plasma creatine kinase	change from before to 8 weeks after intervention initiation
Muscle Damage (safety)	plasma creatine kinase	change from before to 1month after transplant
Patient-reported Fatigue	Anderson Symptom Assessment Scale (range 0-10 where 10 is maximum fatigue)	change from before to 6 months after transplant
Physical Activity	triaxial accelerometry	change from before to 6 months after transplant
6-Minute Walk Test	Mobile application assessment	change from before to 6 months after transplant

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Lindsey J Anderson, PhD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Publications and helpful links

General Publications

• Anderson LJ, Paulsen L, Miranda G, Syrjala KL, Graf SA, Chauncey TR, Garcia JM. Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol. PLoS One. 2024 May 10;19(5):e0302970. doi: 10.1371/journal.pone.0302970. eCollection 2024.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: lymphoma; Hematopoietic Stem Cell Transplant; neuromuscular electrical stimulation; physical function; multiple myeloma; cancer cachexia; muscle wasting; hematologic cancer; cancer rehabilitation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neuromuscular Manifestations; Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Lymphoma; Multiple Myeloma; Muscular Atrophy
• Other Study ID Numbers: F3245-W; IK2RX003245-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes