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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how repetitive transcranial magnetic stimulation (rTMS) might help manage overeating in individuals with Prader-Willi syndrome, a genetic disorder. rTMS is a noninvasive procedure that uses magnetic fields to stimulate the brain and may improve hunger control. The study targets individuals diagnosed with Prader-Willi syndrome. Those with neurological issues, head injuries, or metal implants in their head should not participate. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for 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 prior data suggests that this technique is safe for Prader-Willi syndrome?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe. In past studies, the most common side effects were mild, including tingling at the treatment site (32.1%), skin redness (29.5%), drowsiness (12.5%), and headaches (8.9%). These side effects are not serious and are short-lived. Overall, rTMS has a reassuring safety profile, indicating that most people tolerate it well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to target the brain directly, unlike many treatments for Prader-Willi Syndrome that focus on managing symptoms through medication, behavioral therapy, or dietary control. rTMS uses magnetic fields to stimulate specific areas of the brain, potentially addressing underlying neurological issues rather than just alleviating symptoms. Researchers are excited about this method because it could offer a more direct and possibly faster way to improve cognitive and behavioral functions, presenting a promising alternative to conventional treatments.

What evidence suggests that rTMS is effective for Prader-Willi syndrome?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) might help manage symptoms of Prader-Willi syndrome, such as overeating. In this trial, participants will receive active cerebellum rTMS, which uses a magnetic field to alter brain activity and has been considered a potential aid for weight issues in Prader-Willi syndrome. Some studies suggest that rTMS may be safe and could improve thinking skills and assist with weight control in individuals with this condition. However, the evidence is still developing, and further research is needed to fully understand its effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

Laura Holsen, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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 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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10920723/

Neuromodulation for the treatment of Prader-Willi syndrome Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight.

2. withpower.com withpower.com/trial/phase-prader-willi-syndrome-7-2023-9a6d3

rTMS for Prader-Willi Syndrome Repetitive Transcranial Magnetic Stimulation (rTMS) is generally considered safe for humans, with most studies showing a reassuring safety profile.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35950300/

A potential therapeutic option for obesity in a patient with ... Repetitive transcranial magnetic stimulation: A potential therapeutic option for obesity in a patient with Prader-Willi syndrome.

4. researchgate.net researchgate.net/publication/362628981_Repetitive_Transcranial_Magnetic_Stimulation_a_potential_therapeutic_option_for_obesity_in_a_patient_with_Prader-Willi_syndrome

Repetitive transcranial magnetic stimulation: A potential ... The primary outcome measures of the study included weight changes and cognitive abilities as measured by the Mini-Mental State Examination (MMSE) ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1566070222000145

t-VNS to treat disorders of behaviour in Prader-Willi ... In this paper we review the evidence for the use of tVNS for behavioural problems, consider the challenges when conducting trials in this population, and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05938543

Cerebellar TMS and Satiety in Prader-Willi Syndrome This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study hyperphagia and satiety in Prader-Willi syndrome. TMS is a ...