Neuromodulation for Exercise Adherence

Recruiting at 1 trial location

Overseen By Kalpana P Padala, MD MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Antidepressants, Ototoxic medications

Disqualifiers: Regular physical activity, Wheelchair use, Cognitive impairment, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 26

106 Participants Needed

Trial Summary

What is the purpose of this trial?

Lack of adherence to an exercise program is a major problem for older Veterans. Several fall prevention programs fail in the home setting due to lack of adherence. Exercise adherence is dependent on brain function among other factors. Magnetic stimulation of the front part of the brain improves brain function necessary for planning and following-through. The investigators propose a three-phase study in 106 sedentary older Veterans. Everyone will be trained on use of the exergame, Nintendo Wii-Fit, that the investigators' team has found beneficial in improving balance and gait. They will be asked to exercise using Wii-Fit at home for 45 minutes daily five days/week for 12-weeks. Those that exercise less than recommended dose and those that exercise adequately but have low executive function will receive either real or sham magnetic stimulation to the front part of their brain over ten sessions paired with exercise training. All subjects will further complete 24-weeks of Wii-Fit home exercises. Adherence, executive function, balance and gait, self-efficacy, delay discounting, and falls will be measured periodically.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that increase the risk of seizures, such as bupropion, chlorpromazine, clozapine, and tricyclic antidepressants. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment Neuromodulation for Exercise Adherence?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve motor function in stroke patients and may influence physical activity in those with major depressive disorder, suggesting potential benefits for exercise adherence. ^{1 2 3 4 5}

Is neuromodulation using transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its repetitive (rTMS) and deep (dTMS) forms, is generally considered safe for humans, with most studies showing a reassuring safety profile. However, there have been some reports of adverse events, such as seizures, though these are rare. Overall, TMS is well-tolerated, but monitoring and guidelines are recommended to ensure safety. ^{6 7 8 9 10}

How does the treatment in the Neuromodulation for Exercise Adherence trial differ from other treatments?

The treatment in this trial likely involves neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive method that uses magnetic fields to stimulate nerve cells in the brain. This approach is unique because it targets brain activity directly, unlike traditional exercise adherence methods that may focus on behavioral or motivational strategies. ^{3 5 11 12 13}

Research Team

Kalpana P Padala, MD MS

Principal Investigator

Central Arkansas Veterans Healthcare System , Little Rock, AR

Eligibility Criteria

This trial is for sedentary Veterans aged 60+ who spend a lot of time sitting daily and have a TV at home. It's not for those who are already physically active, use wheelchairs, have significant cognitive impairments, weigh over 325 lbs., or have health conditions that make exercise unsafe. People taking certain medications or with a history of seizures, stroke, bipolar disorder, or abnormal EEGs can't join.

Inclusion Criteria

Subjects reporting spending long periods of time in sedentary behavior by answering affirmatively to the question: 'For most days, do you feel you sit for too long (6-8 hours or more a day)? Some examples might include when watching TV, working at the computer / laptop or when doing sitting-based hobbies such as reading and sewing' will be included

Have TV at home

I am a veteran, 60 years or older, and lead a sedentary lifestyle.

Exclusion Criteria

Those that participate in regular physical activity for at least 30 minutes five or more days of the week

Absolute contraindications to exercise per The American College of Sports Medicine guidelines

Cognitive impairment [Montreal Cognitive Assessment (MoCA < 26)]

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Facility-based Exercise

Participants undergo two weeks of facility-based exercise for safety assessment and learning the program, followed by 12 weeks of home-based exercises.

14 weeks

2 weeks facility-based, 12 weeks home-based

Phase II: rTMS or Sham Treatment

Participants with poor adherence or low executive function receive 10 consecutive weekdays of rTMS or sham treatment along with exercise training.

2 weeks

10 visits (in-person)

Phase III: Home-based Exercise Program

All subjects continue with 24 weeks of a home-based exercise program.

24 weeks

Follow-up

Participants are monitored for adherence, executive function, balance, gait, self-efficacy, delay discounting, and falls.

26 weeks

Assessments at 14, 16, and 40 weeks

Treatment Details

Interventions

• No intervention
• rTMS
• Sham

Trial Overview The study tests if magnetic brain stimulation (rTMS) paired with Nintendo Wii-Fit exercises improves exercise adherence in older adults with executive dysfunction. Participants will train on the Wii-Fit and then receive either real rTMS or sham treatment based on their initial exercise habits and brain function.

Participant Groups

Group I: No intervention Experimental Treatment 1 Intervention

This group will receive no intervention

Group II: rTMS Active Control 1 Intervention

This group will be randomized to receive rTMS

Group III: Sham Placebo Group 1 Intervention

This group will be randomized to receive sham treatment

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 pilot study involving 14 chronic stroke patients, ipsilesional high-frequency rTMS (iHF-rTMS) and contralesional low-frequency rTMS (cLF-rTMS) were tested for their effects on neurophysiological and gait variables, revealing that individual responses to rTMS varied significantly, indicating a need for personalized treatment approaches.

While group-level analysis showed no significant effects of stimulation types on overall outcomes, individual responses correlated with improvements in gait metrics, suggesting that tailored neuromodulation strategies could enhance rehabilitation effectiveness for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Responses to Ipsilesional High-Frequency and Contralesional Low-Frequency rTMS in Chronic Stroke: A Pilot Study to Support the Individualization of Neuromodulation for Rehabilitation. Kindred, JH., Wonsetler, EC., Charalambous, CC., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly improved lower-limb functional outcomes, specifically gait and muscle strength, in individuals with neurological disorders, based on a review of 27 randomized clinical trials.

The treatment showed positive effects for specific conditions like stroke, Parkinson's disease, and spinal cord injury, suggesting rTMS could be a valuable rehabilitation tool, although no improvements were noted for mobility and balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation for improving lower limb function in individuals with neurological disorders: A systematic review and meta-analysis of randomized sham-controlled trials. Krogh, S., Jønsson, AB., Aagaard, P., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has significant potential to enhance neuroplasticity and improve recovery outcomes in the acute phase of stroke, but research in this area is currently limited.

A preliminary trial aimed at studying rTMS in acute stroke was halted due to low patient enrollment, highlighting the need for revised inclusion criteria and policy changes to facilitate better participation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance and Difficulties of Pursuing rTMS Research in Acute Stroke. Carey, JR., Chappuis, DM., Finkelstein, MJ., et al.[2019]

In a study involving 20 stroke patients, neuromuscular electrical stimulation (NMES) combined with repetitive transcranial magnetic stimulation (rTMS) and repetitive facilitative exercise (RFE) significantly improved motor function, as measured by the Fugl-Meyer Assessment and Action Research Arm Test.

The results showed that NMES enhanced the benefits of RFE on hand function, with greater improvements in the Box and Block Test and a reduction in spasticity measured by the Modified Ashworth Scale, indicating that NMES can effectively support rehabilitation efforts for hemiparetic hands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of concomitant neuromuscular electrical stimulation during repetitive transcranial magnetic stimulation before repetitive facilitation exercise on the hemiparetic hand. Etoh, S., Kawamura, K., Tomonaga, K., et al.[2020]

In a pilot study of 14 patients with medication-resistant major depressive disorder, repetitive transcranial magnetic stimulation (rTMS) significantly improved depression symptoms and sleep quality as measured by standard scales, but did not show significant changes in sleep patterns based on actigraphy data.

Interestingly, rTMS treatment led to a notable increase in daily physical activity, with participants taking more steps during the early sessions, suggesting that rTMS may enhance daytime activity levels even if it does not directly improve sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Actigraphy in Patients With Major Depressive Disorder Undergoing Repetitive Transcranial Magnetic Stimulation: An Open Label Pilot Study. Nishida, M., Kikuchi, S., Nisijima, K., et al.[2017]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

In a pilot study involving 28 patients with treatment-resistant depression (TRD), accelerated deep transcranial magnetic stimulation (adTMS) showed significant reductions in depression scores, with a 59% decrease in Hamilton Depression Rating Scale (HDRS) scores after 10 days and 62% after 15 days.

The treatment was found to be safe, with only 9% of patients discontinuing due to adverse events, and 38% to 42% of patients achieving remission, indicating that adTMS could provide rapid clinical benefits and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression. Filipčić, I., Šimunović Filipčić, I., Sučić, S., et al.[2022]

In a study of 210 inpatients receiving either once or twice daily rTMS for major depression, remission rates were similar, with 44.9% for twice daily and 45.4% for daily treatments, indicating comparable effectiveness.

Twice daily rTMS resulted in a significantly shorter length of hospital stay (10.11 days) compared to daily rTMS (18.44 days), suggesting potential cost savings and efficiency in treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression - A large naturalistic retrospective cohort association study. Barnes, R., Skvarc, D., Fitzgerald, PB., et al.[2023]

A systematic review of 61 randomized controlled trials involving 1328 participants with major depressive disorder found a large placebo response (effect size g=0.8) to repetitive transcranial magnetic stimulation (rTMS), indicating that many patients experience significant symptom relief even without active treatment.

The magnitude of the placebo response was linked to the improvement seen in the active treatment group, suggesting that the placebo effect may play a role in the overall therapeutic response to rTMS, and that trial designs may need to account for this effect to better assess the efficacy of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials. Razza, LB., Moffa, AH., Moreno, ML., et al.[2018]

Transcranial static magnetic field stimulation (tSMS) is safe and well-tolerated in children aged 10-18, with no serious adverse effects reported during the study involving 24 participants.

While tSMS did not change cortical excitability in children as it does in adults, it showed potential effects on motor learning, inhibiting early learning and facilitating later stages, suggesting a need for further research in pediatric populations, especially those with conditions like cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Static Magnetic Field Stimulation of the Motor Cortex in Children. Hollis, A., Zewdie, E., Nettel-Aguirre, A., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Individualized Responses to Ipsilesional High-Frequency and Contralesional Low-Frequency rTMS in Chronic Stroke: A Pilot Study to Support the Individualization of Neuromodulation for Rehabilitation. [2022]

2. Sweden pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation for improving lower limb function in individuals with neurological disorders: A systematic review and meta-analysis of randomized sham-controlled trials. [2022]

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

Importance and Difficulties of Pursuing rTMS Research in Acute Stroke. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of concomitant neuromuscular electrical stimulation during repetitive transcranial magnetic stimulation before repetitive facilitation exercise on the hemiparetic hand. [2020]

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

Actigraphy in Patients With Major Depressive Disorder Undergoing Repetitive Transcranial Magnetic Stimulation: An Open Label Pilot Study. [2017]

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

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. [2022]

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

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression - A large naturalistic retrospective cohort association study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Static Magnetic Field Stimulation of the Motor Cortex in Children. [2022]