Accelerated rTMS for Post-Stroke Apathy

Overseen By Lisa McTeague, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical University of South Carolina

Disqualifiers: Dementia, Aphasia, Seizure disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to treat apathy (lack of interest or motivation) in individuals who have experienced a stroke. Researchers use the MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System to deliver targeted magnetic pulses to the brain. The goal is to determine if this method is safe and can effectively reduce apathy symptoms. Individuals who had a stroke over six months ago and are experiencing noticeable apathy might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this device is safe for treating post-stroke apathy?

Research shows that transcranial magnetic stimulation (TMS), like the kind used in this study, is generally safe. The most common side effects are mild and temporary, such as slight discomfort or a tingling sensation at the treatment site. The MagVenture MagPro TMS System, used in this study, has been employed in other research and is designed for both clinical and research purposes.

Although this study is in its early stages, the treatment uses a system tested for other conditions. In those situations, it has been well-tolerated. While this treatment is new for post-stroke apathy, the TMS technology itself has a history of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for post-stroke apathy, which often include medications like antidepressants or psychotherapy, the MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System offers a non-invasive, brain-targeted approach. This treatment is unique because it uses repetitive transcranial magnetic stimulation (rTMS) to directly stimulate the medial prefrontal cortex (mPFC), a brain area linked to motivation and emotion regulation. Researchers are excited about this treatment because it delivers high-dose stimulation quickly over just a few days, which might lead to faster improvements compared to traditional therapies that can take weeks or months to show effects.

What evidence suggests that this rTMS treatment might be effective for post-stroke apathy?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) holds promise for treating apathy after a stroke. Past studies demonstrated that high-frequency rTMS reduced apathy symptoms in long-term stroke survivors. This trial will provide all participants with accelerated, high-dose rTMS targeting the medial prefrontal cortex (mPFC). The treatment uses magnetic fields to stimulate brain cells, focusing on areas that affect mood and motivation. Although more research is needed to fully understand the results, earlier findings suggest that rTMS can significantly improve motivation and interest in those affected by a stroke. This offers hope for enhancing the quality of life for these individuals. ^{2 4 5 6 7}

Who Is on the Research Team?

Parneet Grewal, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals over 40 who've had a stroke at least 6 months ago and are experiencing apathy. They must be able to do cognitive tests, have an intact cortex in the target area confirmed by imaging, and score high on specific apathy scales. Excluded are those with other major neurological issues, severe communication problems, psychotic disorders, recent suicidality or substance abuse, pregnancy, MRI or TMS contraindications like pacemakers or metal implants.

Inclusion Criteria

I can take part in mental health and thinking tests.

I am 40 years old or older.

You are showing signs of not caring about things.

Exclusion Criteria

You feel very uncomfortable in small spaces and can't have an MRI scan.

I do not have implants or devices that could be affected by MRI or TMS.

You have bleeding outside the brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo structural and resting state functional MRI and a battery of clinical assessments

1 week

1 visit (in-person)

Treatment

Participants receive high-dose rTMS to left mPFC, 600 pulses, twelve times per day, for three treatment days within a seven-day period

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with weekly assessments for one month

4 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System

Trial Overview The study is testing whether a high-dose version of rTMS (a non-invasive brain stimulation technique) can reduce symptoms of apathy in people who have had a stroke. The treatment targets the medial prefrontal cortex and aims to see if it's safe and effective when given at an accelerated pace.

How Is the Trial Designed?

Group I: Repetitive transcranial magnetic stimulation Experimental Treatment 1 Intervention

All participants will receive accelerated, high-dose repetitive transcranial magnetic stimulation (rTMS) at the medial prefrontal cortex (mPFC) delivered in runs of 600 pulses, twelve times per day, for three treatment days (contiguous or non-contiguous) within a seven-day period.

MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System is already approved in European Union, United States for the following indications:

Approved in European Union as MagVenture MagPro TMS System for:

• Depression
• Obsessive Compulsive Disorder (OCD)
• Addiction

Approved in United States as MagVenture MagPro TMS System for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder (OCD)
• Chronic Pain

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) has been shown to have a very low incidence of side effects, with the most serious being seizures, which often occurred when stimulation parameters were not followed or when combined with medications that lower seizure thresholds.

The expert consensus indicates that repetitive TMS (rTMS) is effective for treating chronic neuropathic pain, major depressive episodes, and auditory hallucinations, suggesting it has a strong therapeutic indication in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. Lefaucheur, JP., André-Obadia, N., Poulet, E., et al.[2022]

Accelerated transcranial magnetic stimulation (TMS) protocols, which involve multiple sessions per day over a few days, aim to enhance the effectiveness of treatment for major depressive disorder (MDD) and reduce the overall treatment duration compared to conventional TMS.

The review highlights that while accelerated TMS shows promise in improving antidepressant efficacy and safety, nearly half of MDD patients still do not respond to TMS, indicating a need for further research and optimization of treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief? Tang, N., Shu, W., Wang, HN.[2023]

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]

Repetitive transcranial magnetic stimulation (rTMS) has shown a positive impact on apathy in patients with Alzheimer's disease and some potential benefits in chronic stroke, suggesting it may be a feasible treatment option for these conditions.

The safety of rTMS was confirmed across various studies, but its efficacy varied significantly among different neurodegenerative conditions, with limited evidence of effectiveness in Parkinson's disease and mild traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review. Espiritu, AI., Hara, T., Tolledo, JK., et al.[2023]

In a pilot study involving 6 patients with post-stroke depression, an accelerated rTMS protocol significantly reduced depression scores (HAMD) from an average of 15.5 to 4.17, with effects lasting up to 3 months after treatment.

The study found that the accelerated rTMS treatment was safe, with no significant adverse events reported, suggesting it could be a viable alternative or adjunctive therapy for post-stroke depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel TMS for Stroke and Depression (NoTSAD): Accelerated Repetitive Transcranial Magnetic Stimulation as a Safe and Effective Treatment for Post-stroke Depression. Frey, J., Najib, U., Lilly, C., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has shown positive effects on post-stroke aphasia rehabilitation in 12 studies, indicating it can enhance recovery when used alongside conventional therapies or even alone.

No adverse effects were reported in the studies reviewed, suggesting that rTMS is a safe intervention; however, further large-scale, well-designed trials are needed to confirm its efficacy and establish it as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on post-stroke aphasia. Wong, IS., Tsang, HW.[2019]

Repetitive transcranial magnetic stimulation (rTMS) was successfully used to treat a case of poststroke apathy, which is often detrimental to patient recovery.

Improvements in the patient's condition were linked to enhanced interhemispheric functional connectivity, suggesting that rTMS may facilitate better communication between the brain's hemispheres, aiding recovery from apathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Repetitive Transcranial Magnetic Stimulation for Poststroke Apathy Is Associated with Improved Interhemispheric Functional Connectivity. Mitaki, S., Onoda, K., Abe, S., et al.[2017]

In a study involving 13 chronic stroke patients, high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improved apathy and depression scores compared to a sham stimulation group, indicating its potential efficacy for treating apathy post-stroke.

The rTMS was applied over the dorsal anterior cingulate cortex and medial prefrontal cortex, suggesting that targeting these brain regions may be beneficial for addressing apathy in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients. Sasaki, N., Hara, T., Yamada, N., et al.[2018]

In a study of 20 stroke patients over 4 months, transcranial magnetic stimulation (TMS) revealed significant improvements in motor cortical output, particularly in the first 80 days post-stroke, indicating ongoing neural plasticity during rehabilitation.

The affected hemisphere showed a decrease in excitability threshold and improvements in motor evoked potentials, suggesting that neuro-rehabilitation can lead to meaningful recovery in motor function even months after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurophysiological follow-up of motor cortical output in stroke patients. Traversa, R., Cicinelli, P., Oliveri, M., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07113067

Accelerated rTMS vs. Sham for Stroke Apathy Furthermore, rTMS is especially promising for post-stroke apathy (PSA) as it provides the flexibility for personalizing TMS coil placement in relation to post- ...

2. withpower.com withpower.com/trial/accelerated-rtms-for-post-stroke-apathy-7b8c4

Accelerated rTMS for Post-Stroke Apathy This pilot study will investigate the safety, feasibility, tolerability, and preliminary efficacy of accelerated high-dose repetitive transcranial magnetic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05878457

NCT05878457 | Accelerated rTMS for Post-Stroke Apathy This pilot study will investigate the safety, feasibility, tolerability, and preliminary efficacy of accelerated high-dose repetitive transcranial magnetic ...

4. karger.com karger.com/ene/article/78/1-2/28/125304/The-Efficacy-of-High-Frequency-Repetitive

The Efficacy of High-Frequency Repetitive Transcranial ... The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients Available.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306417/

Efficacy and Safety of Transcranial Magnetic Stimulation on ... We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer disease (AD), AD-related dementias, and nondementia ...

6. magventure.com magventure.com/us/safety-information/

Safety information - MagVenture US Safety information. Magnetic stimulation is considered a safe procedure with the most common side effects being relatively mild and transient.

7. magventure.com magventure.com/us/products/magpro-r30/

MagPro R30 - MagVenture US The MagPro R30 is a high-performance TMS stimulator primarily for clinical use as well as research. A diagnostic for therapeutic treatment.