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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the idea that Muscle Stimulation for Stem Cell Transplant Recovery is an effective treatment?

The available research shows that Muscle Stimulation, also known as Neuromuscular Electrical Stimulation (NMES), is effective in strengthening weak muscles and improving muscle function. For example, one study highlights that NMES can help increase muscle strength by generating muscle forces during training. Another study indicates that NMES can activate paralyzed muscles in people with spinal cord injuries, leading to improvements in muscle mass and function. Although these studies focus on different conditions, they suggest that NMES can be beneficial in enhancing muscle recovery and function, which could be relevant for stem cell transplant recovery as well. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment RS-4i Plus Sequential Stimulator for muscle recovery?

Research shows that neuromuscular electrical stimulation (NMES) can strengthen weak muscles and improve muscle function, which may help in recovery after stem cell transplants. NMES has been effective in increasing muscle strength and function in various conditions, including spinal cord injuries. ^{1 2 3 4 5}

What safety data exists for muscle stimulation treatments?

The safety of neuromuscular electrical stimulation (NMES) has been evaluated in various studies. A study on critical ill patients found NMES to be safe and feasible. Another pilot safety study on patients with implantable cardioverter defibrillators (ICDs) showed that long-term NMES of thigh muscles was safe, with no adverse events or ICD function abnormalities observed. These findings suggest that NMES is generally safe, but individual risk assessments are recommended. ^{1 2 3 6 7}

Is neuromuscular electrical stimulation (NMES) safe for humans?

Research indicates that neuromuscular electrical stimulation (NMES) is generally safe for humans, including those with implantable cardioverter defibrillators (ICDs), as long as individual risks are assessed beforehand. In a study involving long-term NMES, no adverse events were reported, and ICD function remained normal. ^{1 2 3 6 7}

Is the treatment in the trial 'Muscle Stimulation for Stem Cell Transplant Recovery' a promising treatment?

Yes, the treatment, known as neuromuscular electrical stimulation (NMES), is promising because it helps strengthen weak muscles, improve muscle function, and provide health benefits similar to exercise. ^{1 2 3 4 8}

How does the treatment 'Muscle Stimulation for Stem Cell Transplant Recovery' differ from other treatments for this condition?

This treatment uses neuromuscular electrical stimulation (NMES), which is a technique that applies electrical impulses to muscles to help them contract and strengthen. Unlike traditional treatments, NMES can be used to improve muscle function and recovery without the need for physical exercise, making it particularly useful for patients who are unable to engage in regular physical activity. ^{1 2 3 4 8}

Research Team

Lindsey J Anderson, PhD

Principal Investigator

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

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A new paradigm of neuromuscular electrical stimulation for the quadriceps femoris muscle. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Development and reliability of a new system for bedside evaluation of non-volitional knee extension force. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of maximum tolerated muscle torques produced by 2 pulse durations. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Neuromuscular Electrical Stimulation-Induced Resistance Training After SCI: A Review of the Dudley Protocol. [2018]

5. Denmark pubmed.ncbi.nlm.nih.gov

Acute effects of conventional versus wide-pulse neuromuscular electrical stimulation on quadriceps evoked torque and neuromuscular function. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and feasibility of a neuromuscular electrical stimulation chronaxie-based protocol in critical ill patients: A prospective observational study. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study. [2022]

8. Brazil 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. [2023]