rTMS for Prader-Willi Syndrome

Overseen By Laura Holsen, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Neurological disorder, Head trauma, Seizures, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study hyperphagia and satiety in Prader-Willi syndrome. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study, the investigators will be stimulating the brain to learn more about how TMS might improve hyperphagia in Prader-Willi syndrome.

Do I need to stop my current medications for the trial?

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Prader-Willi Syndrome?

Research shows that rTMS can improve symptoms in children with Tourette syndrome and reduce muscle spasticity in cerebral palsy, suggesting it may have potential benefits for other neurological conditions like Prader-Willi Syndrome. ^{1 2 3 4 5}

Is rTMS generally safe for humans?

Repetitive Transcranial Magnetic Stimulation (rTMS) is generally considered safe for humans, with most studies showing a reassuring safety profile. Known side effects can include headaches, local pain, and in rare cases, seizures, but guidelines have been developed to minimize these risks. ^{1 6 7 8 9}

How does the treatment rTMS differ from other treatments for Prader-Willi Syndrome?

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment that uses magnetic fields to stimulate specific areas of the brain. Unlike traditional drug treatments, rTMS targets the brain directly and has been used successfully in other conditions like Tourette syndrome to improve symptoms by modulating brain activity. This makes it a novel approach for conditions like Prader-Willi Syndrome, where standard treatments may not be well-established. ^{1 3 10 11 12}

Research Team

Laura Holsen, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for individuals with Prader-Willi syndrome. Participants must not have a history of neurological disorders, head trauma with unconsciousness, seizures or epilepsy (including in close relatives), metal in the brain or skull, implanted medical devices like pacemakers, or claustrophobia in MRI machines.

Inclusion Criteria

I have been diagnosed with Prader-Willi syndrome.

Exclusion Criteria

You have had a head injury that made you lose consciousness.

You have a medical device implanted in your body, like a pacemaker or nerve stimulator.

I have a history of seizures, epilepsy, or a close family member with epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cerebellar targeted iTBS once daily for one week

1 week

7 visits (in-person)

Follow-up

Participants are monitored for changes in BOLD response and retention of subjects in study assessments

1 week

1 visit (in-person)

Enrollment

Time required to enroll the target sample size into the study

Up to 18 months

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study is testing repetitive Transcranial Magnetic Stimulation (rTMS) on participants to see if it can help control excessive hunger and improve feelings of fullness in those with Prader-Willi syndrome. rTMS uses magnetic fields to stimulate brain activity noninvasively.

Participant Groups

Group I: Active cerebellum rTMS Experimental Treatment 1 Intervention

Cerebellar targeted iTBS, once daily, one week

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Foundation for Prader-Willi Research

Collaborator

Trials

14

Recruited

1,200+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a safe and tolerable treatment option for various pediatric neurological disorders, showing therapeutic benefits in conditions like adolescent depression and hemiparesis from pediatric stroke.

While rTMS has shown promise in some areas, such as autism and tics/Tourette syndrome, more high-quality studies are needed, especially for conditions like migraine in children, where evidence is still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for the Treatment of Pediatric Neurological Disorders. Malone, LA., Sun, LR.[2020]

Transcranial brain stimulation techniques, especially TMS and tDCS, show promise in treating various pediatric neurological and psychiatric disorders, including autism spectrum disorder and ADHD.

TMS has been effectively used as an experimental tool in children with conditions like perinatal stroke and depression, while tDCS has been explored for its therapeutic potential in disorders such as epilepsy and cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic and Direct Current Stimulation in Children. Hameed, MQ., Dhamne, SC., Gersner, R., et al.[2018]

In a study involving 25 children with Tourette syndrome, 20 daily sessions of 1 Hz rTMS targeted at the supplemental motor area significantly reduced tic severity and improved various clinical symptoms for at least six months after treatment.

The improvements in tic severity were associated with increased resting motor thresholds, indicating a potential mechanism of action for rTMS in enhancing motor control in children with TS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. Le, K., Liu, L., Sun, M., et al.[2013]

In a study involving 26 adult patients with ADHD, bilateral deep transcranial magnetic stimulation (dTMS) did not show any significant clinical benefits compared to sham treatment, indicating it may not be an effective therapy for adult ADHD.

The study highlights the need for caution in interpreting these results due to the small sample size, suggesting that further research is necessary to fully understand the potential of dTMS in treating ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised sham-controlled study of high-frequency bilateral deep transcranial magnetic stimulation (dTMS) to treat adult attention hyperactive disorder (ADHD): Negative results. Paz, Y., Friedwald, K., Levkovitz, Y., et al.[2022]

In a study involving 30 spastic cerebral palsy patients, repetitive TMS (rTMS) therapy significantly improved motor function, with the greatest gains observed in those receiving 40 therapy sessions (4.27% increase in GMFM score).

All groups experienced a notable reduction in muscle spasticity, indicating that rTMS is effective in modulating both motor activity and spasticity in children with cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing Number of Therapy Sessions of Repetitive Transcranial Magnetic Stimulation Improves Motor Development by Reducing Muscle Spasticity in Cerebral Palsy Children. Rajak, BL., Gupta, M., Bhatia, D., 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 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]

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]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

In a pilot study involving 10 male children with Tourette's syndrome, repetitive transcranial magnetic stimulation (rTMS) applied to the supplementary motor area (SMA) resulted in significant improvements in tic symptoms over 12 weeks, as measured by the Yale Global Tourette's Syndrome Severity Scale and Clinical Global Impression.

The treatment was well-tolerated with no reported side effects or worsening of ADHD, depressive, or anxiety symptoms, suggesting that rTMS is a safe and potentially effective intervention for managing tics in children with Tourette's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette's syndrome. Kwon, HJ., Lim, WS., Lim, MH., et al.[2011]

In a study involving 30 patients with Tourette syndrome, low-frequency rTMS targeting the bilateral parietal cortex significantly reduced motor and phonic tics, as well as premonitory urges, with improvements lasting for at least one month after treatment.

The active rTMS group showed marked symptom relief compared to the sham group, indicating that this non-invasive treatment could be a promising option for patients who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome. Fu, M., Wei, H., Meng, X., et al.[2021]

In a phase 1 clinical trial involving 10 children with Tourette syndrome, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area significantly reduced tic severity, as indicated by a decrease in the Yale Global Tic Severity Scale score (p<0.001).

The rTMS treatment was well-tolerated by all participants, demonstrating that this method is feasible and safe for use in children with Tourette syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. Kahl, CK., Kirton, A., Pringsheim, T., et al.[2021]

References

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

Transcranial Magnetic Stimulation for the Treatment of Pediatric Neurological Disorders. [2020]

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

Transcranial Magnetic and Direct Current Stimulation in Children. [2018]

3. Scotland pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Randomised sham-controlled study of high-frequency bilateral deep transcranial magnetic stimulation (dTMS) to treat adult attention hyperactive disorder (ADHD): Negative results. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Increasing Number of Therapy Sessions of Repetitive Transcranial Magnetic Stimulation Improves Motor Development by Reducing Muscle Spasticity in Cerebral Palsy Children. [2022]

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

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

7. 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]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

10. Ireland pubmed.ncbi.nlm.nih.gov

1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette's syndrome. [2011]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome. [2021]

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

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. [2021]