Muscle Stimulation for Stem Cell Transplant Recovery

Overseen By Jose M Garcia, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Anabolic agents

Disqualifiers: Deep vein thrombosis, Hemorrhagic disorders, Liver cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve recovery after stem cell transplants for certain blood cancers. It tests a device that uses electrical stimulation to keep muscles active, potentially preventing the muscle loss and fatigue common after such treatments. Participants will use the RS-4i Plus Sequential Stimulator, a neuromuscular electrical stimulation device, to deliver gentle electrical pulses to their muscles. Veterans planning to undergo autologous stem cell transplants for these cancers and who meet specific health criteria are ideal candidates for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative recovery methods and potentially enhance post-transplant outcomes.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are using anabolic agents or are part of other nutritional or physical exercise trials.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using anabolic agents, you cannot participate in this trial.

What prior data suggests that this neuromuscular electrical stimulation is safe for stem cell transplant recovery?

Research has shown that neuromuscular electrical stimulation (NMES) is generally safe. The RS-4i Plus Sequential Stimulator, the device used in this trial, helps relax muscles, prevent muscle loss, and maintain muscle health. Previous studies on this type of muscle stimulation have not identified any major safety issues.

The device also employs high-frequency therapy to relieve pain, which has been used without causing serious side effects. Participants in similar studies have tolerated the stimulation well, experiencing only mild discomfort similar to exercise.

Overall, the available safety data suggest that NMES is a well-tolerated method to improve physical function after stem cell transplants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the RS-4i Plus Sequential Stimulator for stem cell transplant recovery because it offers a novel approach to aid recovery through muscle stimulation. Unlike traditional methods that mainly focus on medication and physical therapy, this technique uses neuromuscular electrical stimulation (NMES) to directly stimulate muscles, potentially enhancing recovery speed and effectiveness. The active NMES delivers asymmetric biphasic waveforms, encouraging muscle contractions without pain, which is a departure from standard care options that do not actively engage muscle tissues in this manner. This method could redefine post-transplant rehabilitation by potentially reducing recovery time and improving muscle function more efficiently.

What evidence suggests that neuromuscular electrical stimulation is effective for recovery after stem cell transplant?

In this trial, participants will join different treatment arms to evaluate the effectiveness of muscle stimulation during stem cell transplant recovery. Previous studies have shown that electrical stimulation on muscles can strengthen weak muscles and improve their function. This is especially beneficial for individuals recovering from stem cell transplants, as it helps them remain physically active and maintain their quality of life. Research indicates that this method can reduce negative effects of transplants, such as muscle loss and fatigue. Devices like the RS-4i Plus Sequential Stimulator, used by participants in the active NMES arm, can keep muscles active without requiring traditional exercise. This approach may be particularly useful for those who find regular physical activity challenging after a transplant. ^{2 3 4 5 6}

Who Is on the Research Team?

Lindsey J Anderson, PhD

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Are You a Good Fit for This Trial?

This trial is for Veterans planning to undergo autologous stem cell transplant at VAPSHCS and can consent. It's not for those with active blood clots, untreated bleeding disorders, muscle conditions that forbid electrical stimulation, heart devices, severe liver or kidney disease, previous stem cell transplants, or high baseline muscle soreness.

Inclusion Criteria

I am a veteran enrolled for a stem cell transplant at VAPSHCS.

I understand and can communicate my decision to participate.

Exclusion Criteria

I have a bleeding disorder that hasn't been treated.

I have never had rhabdomyolysis or muscle conditions that prevent NMES use.

I am currently using anabolic agents.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo neuromuscular electrical stimulation (NMES) or Sham intervention during hematopoietic cell transplantation (HCT) to maintain physical function and quality of life

4 weeks

Multiple sessions (in-person)

Follow-up 1

Participants are assessed for physical function, body composition, and quality of life 28 days after HCT

4 weeks

1 visit (in-person)

Follow-up 2

Participants are monitored for recovery of physical function, quality of life, and fatigue 6 months after HCT

6 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RS-4i Plus Sequential Stimulator

Trial Overview The study tests neuromuscular electrical stimulation (NMES) using the RS-4i Plus Sequential Stimulator to maintain physical function and quality of life after a hematologic stem cell transplant. The goal is to see if NMES can help reduce deconditioning and fatigue from cancer treatment.

How Is the Trial Designed?

Group I: Active NMES Active Control 1 Intervention

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.

Group II: Sham NMES Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

The newly developed NMES-dynamometer system demonstrated high reliability for assessing knee extensor muscle function, with intra-rater correlation coefficients of 0.91 for maximal voluntary force and 0.94 for supramaximal twitch force, indicating consistent results across different testing sessions.

Inter-rater reliability was also strong, with coefficients of 0.89 and 0.86 for the same measures, suggesting that different raters can use this system effectively to evaluate muscle function with minimal variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and reliability of a new system for bedside evaluation of non-volitional knee extension force. Vaz, MA., Fröhlich, M., Júnior, DPDS., et al.[2022]

In a study involving 10 adults, neuromuscular electrical stimulation (NMES) with a 200-microsecond pulse duration allowed participants to tolerate significantly greater muscle torques compared to a 50-microsecond pulse duration, indicating enhanced efficacy for muscle strengthening.

The findings suggest that medium pulse durations may be more effective for maximizing muscle torque responses, despite the common belief that shorter pulses are preferable due to lower pain thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of maximum tolerated muscle torques produced by 2 pulse durations. Scott, WB., Causey, JB., Marshall, TL.[2014]

In a study involving 24 healthy males, neuromuscular electrical stimulation (NMES) with wide phase durations (500 µs) produced significantly greater torque compared to narrow phase durations (200 µs), indicating that longer phase durations may enhance muscle activation during rehabilitation.

While both KHz frequency alternating currents and pulsed currents showed similar effectiveness in evoking muscle torque, the 500 µs phase duration resulted in higher discomfort levels, suggesting a trade-off between effectiveness and comfort in NMES applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of different electrical stimulation currents and phase durations on submaximal and maximum torque, efficiency, and discomfort: a randomized crossover trial. Pinto Damo, NL., Modesto, KA., Neto, IVS., et al.[2023]

In a study involving 17 young men, both conventional and wide-pulse neuromuscular electrical stimulation (NMES) protocols produced similar levels of evoked torque, indicating that either method can be effective for muscle stimulation.

All NMES protocols led to significant muscle fatigue, but the underlying changes were primarily peripheral rather than central, suggesting that both types of NMES may have comparable long-term effects on muscle function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of conventional versus wide-pulse neuromuscular electrical stimulation on quadriceps evoked torque and neuromuscular function. Espeit, L., Luneau, E., Brownstein, CG., et al.[2023]

The neuromuscular electrical stimulation (NMES) protocol applied to critical ill patients was found to be safe, with no significant changes in muscle damage markers (creatine phosphokinase) or other safety indicators (central venous oxygen saturation and serum lactate) over the study period.

The NMES protocol was also feasible, with patients completing 85% of the planned sessions in an average time of 107 minutes, indicating that this treatment can be effectively integrated into the care of critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of a neuromuscular electrical stimulation chronaxie-based protocol in critical ill patients: A prospective observational study. Silva, PE., Babault, N., Mazullo, JB., et al.[2018]

A resistance training form of neuromuscular electrical stimulation (NMES) was successfully applied to individuals with motor complete spinal cord injury, leading to significant increases in muscle mass averaging 30% to 40% over 3 to 6 months of training.

Participants experienced no adverse events and showed consistent progress in their ability to perform more repetitions and lift heavier weights, indicating that NMES can effectively stimulate muscle growth and function even years after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular Electrical Stimulation-Induced Resistance Training After SCI: A Review of the Dudley Protocol. Bickel, CS., Yarar-Fisher, C., Mahoney, ET., et al.[2018]

In a study involving 10 healthy subjects, neuromuscular electrical stimulation with large electrodes and multiple current pathways (m-NMES) produced greater muscle contractions compared to conventional NMES (c-NMES).

m-NMES was also associated with lower discomfort levels during stimulation, making it a more comfortable option for quadriceps muscle training, while fatigue levels were similar between both methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm of neuromuscular electrical stimulation for the quadriceps femoris muscle. Maffiuletti, NA., Vivodtzev, I., Minetto, MA., et al.[2021]

A pilot safety study involving six patients with implantable cardioverter defibrillators (ICDs) showed that long-term neuromuscular electrical stimulation (NMES) of thigh muscles is safe, with no adverse events reported during the treatment.

All patients received a total of over 14 million electrical pulses without any abnormalities in ICD function, suggesting that NMES can be a viable option for improving muscle strength and endurance in patients with chronic heart failure who have ICDs, provided individual risks are assessed beforehand.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study. Crevenna, R., Wolzt, M., Fialka-Moser, V., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-3-4-2021-40d98

Muscle Stimulation for Stem Cell Transplant Recovery Research shows that neuromuscular electrical stimulation (NMES) can strengthen weak muscles and improve muscle function, which may help in recovery after stem ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04364256

Muscle Stimulation for Physical Function During Stem Cell ... The investigators are testing an alternative exercise strategy, neuromuscular electrical stimulation, to maintain physical function quality of life after HCT.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11086915/

Neuromuscular electrical stimulation for physical function ... Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0302970

Neuromuscular electrical stimulation for physical function ... Neuromuscular electrical stimulation will attenuate hematopoietic stem cell transplant-induced adverse effects on physical function, muscle mass, quality of ...

5. rsmedical.com rsmedical.com/rs4iplus

RS-4i Plus The RS-4i Plus Sequential Stimulator uniquely combines true high frequency (5000 Hz) Interferential therapy for long-lasting pain relief.

6. accessdata.fda.gov accessdata.fda.gov/scripts/cdrh/cfdocs/cfres/res.cfm?id=91463

Class 2 Device Recall RS4i Sequential Stimulator; Powered MUSCLE Stimulation indications for use including: 1) Relax muscle spasm. 2) Prevention or retardation of disuse atrophy. 3) Maintain or ...