Brain Stimulation for Gastrointestinal Disorders

Overseen By Paul HM Kullmann, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: David Levinthal

Must not be taking: Tricyclics, Antipsychotics, Stimulants, others

Disqualifiers: Diabetes, Head injury, Pregnancy, 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: 1

Duration: Multiple sessions

244 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a non-invasive brain stimulation technique called rTMS on healthy people and those with IBS or FD. The goal is to see if it can help regulate automatic body functions like digestion and heart rate by changing brain activity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has been used to treat various neurological and psychiatric conditions, including major depression, migraine-associated headaches, and obsessive-compulsive disorder.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that can lower the seizure threshold, such as some antidepressants and recreational drugs. If you are on any of these, you would need to stop them to participate.

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used within recommended guidelines, with common side effects being minor, such as headaches. There is a low risk of seizures, and long-term effects are not fully known, but safety guidelines have been established to minimize risks. ^{1 2 3 4 5}

How is the treatment rTMS different from other treatments for gastrointestinal disorders?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially altering brain activity to help manage symptoms. Unlike traditional drug treatments, rTMS directly targets brain circuits and can have lasting effects beyond the stimulation period, offering a novel approach for conditions like gastrointestinal disorders where standard treatments may not exist. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment rTMS for gastrointestinal disorders?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce visceral sensation and emotional response in the gut, which may help with conditions like irritable bowel syndrome (IBS). This suggests that rTMS might be effective in modifying brain-gut interactions and improving gastrointestinal symptoms. ^{9 10 11 12 13}

Who Is on the Research Team?

David J Levinthal, MD/PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults aged 21-60 with gastrointestinal issues like functional dyspepsia or irritable bowel syndrome, as well as healthy individuals without these symptoms. It's not for pregnant people, those with a BMI over 35, metal implants, history of gastric surgery, heavy alcohol use, certain medication users, or those with heart problems.

Inclusion Criteria

I do not have any stomach or intestinal problems.

I am between 21 and 60 years old.

I have symptoms like those of irritable bowel syndrome or functional dyspepsia.

Exclusion Criteria

I have had a head injury, stroke, seizures, or metal in my skull.

I have had a heart attack, need extra oxygen, or have diabetes.

I am not currently using medications or substances known to lower seizure threshold.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Session

Measures of autonomic activity (EGG, ECG, CI) are monitored before and after consumption of a test meal, water, or a nutrient drink. MEPs are assessed before and after the meal or drink.

1 session

1 visit (in-person)

Treatment

Repetitive transcranial magnetic stimulation (rTMS) is applied before the meal or drink. Responses to symptom surveys are used to characterize subjects.

Multiple sessions

Multiple visits (in-person)

Follow-up

Participants are monitored for changes in physiological reactivity and correlated with assessments of disease severity, mood, and quality of life.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests the effects of rTMS (repetitive Transcranial Magnetic Stimulation), a non-invasive brain stimulation technique on autonomic regulation and gastrointestinal function to develop new treatments for GI disorders.

How Is the Trial Designed?

Group I: Study subjects Experimental Treatment 1 Intervention

At the baseline session, measures of autonomic activity (electrogastrogram - EGG, electrocardiogram - ECG, cardiac impedance - CI) will be monitored from about 15 minutes before up to 1 hour after consumption of a test meal, water or a nutrient drink. In addition, motor-evoked potentials (MEPs) elicited with single pulse transcranial magnetic stimulation will be assessed before and after the meal or drink. In subsequent sessions, repetitive transcranial magnetic stimulation (rTMS) is applied before the meal or drink. Based on responses to symptom surveys (IBS-SSS and PAGI-SYM), study subjects will be characterized as healthy or as having functional dyspepsia and/or IBS.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

David Levinthal

Lead Sponsor

Trials

2

Recruited

260+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive brain stimulation technique that can enhance brain excitability and potentially improve conditions like stroke, Parkinson's disease, and depression, as discussed in a 2010 symposium with insights from both animal studies and small clinical trials.

While there is significant interest and some signs of therapeutic success with rTMS, the current models explaining its effects may need refinement to fully understand the underlying mechanisms and outcomes observed in various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know? Platz, T., Rothwell, JC.[2013]

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]

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) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[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]

In a study of 22 patients with acute ischaemic stroke, active repetitive transcranial magnetic stimulation (rTMS) significantly improved dysphagia compared to sham treatment, indicating its potential effectiveness in treating swallowing difficulties after brainstem infarctions.

The improvements in dysphagia were sustained for up to 2 months, suggesting that rTMS could be a valuable addition to rehabilitation strategies for patients with lateral medullary infarction and other brainstem strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic role of rTMS on recovery of dysphagia in patients with lateral medullary syndrome and brainstem infarction. Khedr, EM., Abo-Elfetoh, N.[2017]

Transcranial magnetic stimulation (TMS) is a safe and noninvasive technique that can disrupt brain function to study the prefrontal cortex's role in cognitive functions like working memory and language.

Repetitive TMS has been effectively used to treat medication-resistant depression by stimulating the left dorsolateral prefrontal cortex, and research is ongoing to explore its potential for other conditions like stroke and Alzheimer's disease, although most applications are not yet FDA-approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: Neurophysiological and clinical applications. Burke, MJ., Fried, PJ., Pascual-Leone, A.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo-controlled pilot study. [2014]

2. Ireland pubmed.ncbi.nlm.nih.gov

Modification of rectal function and emotion by repetitive transcranial magnetic stimulation in humans. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019]

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

Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know? [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

Effect of repetitive transcranial magnetic stimulation on rectal function and emotion in humans. [2021]

6. 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]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

10. 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]

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

Therapeutic role of rTMS on recovery of dysphagia in patients with lateral medullary syndrome and brainstem infarction. [2017]

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

Preliminary evidence of the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing functions in post-stroke individuals with chronic dysphagia. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: Neurophysiological and clinical applications. [2020]