TMS for Anorexia

Overseen By Megan Shott, BS

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Anticonvulsants, Tricyclics, Neuroleptics, others

Disqualifiers: Pregnancy, Seizures, Head trauma, 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: 6

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for anorexia nervosa using transcranial magnetic stimulation (TMS), which uses magnetic fields to stimulate specific brain areas. Anorexia nervosa is a serious condition characterized by a distorted body image and fear of weight gain, often resulting in severe weight loss. The trial seeks to determine if TMS can alter certain brain circuits associated with these symptoms and improve behaviors related to anorexia. It includes two groups: one receiving active TMS and another receiving a sham treatment that mimics the real one. Females aged 18 to 45 with a current diagnosis of anorexia nervosa and no significant health issues may be suitable for this trial. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for anorexia nervosa.

Will I have to stop taking my current medications?

The trial requires that participants do not take more than 2 mg of lorazepam daily or any anticonvulsants, and they cannot be on certain antidepressants like bupropion, tricyclic antidepressants, or neuroleptics. If you are on these medications, you may need to stop or adjust them to participate.

What prior data suggests that this TMS treatment is safe for anorexia nervosa?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe for people with anorexia nervosa. Studies have found that TMS can improve symptoms with only minor and short-lived side effects, such as mild headaches or scalp discomfort, which typically do not last long.

Previous research suggests that TMS is well-tolerated, with most people not experiencing serious negative reactions. Although larger studies are still needed for more detailed information, current evidence supports TMS as a safe option for treating anorexia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the rTMS treatment using the BrainsWay Model 104 system for anorexia because it offers a non-invasive approach that directly targets brain activity. Unlike traditional treatments such as psychotherapy and medication, this method uses a specialized H1-Coil to deliver repetitive transcranial magnetic stimulation (rTMS) to specific areas of the brain, potentially altering neural pathways involved in anorexia. The technique's precision in targeting the left dorsolateral prefrontal cortex (DLPFC) could lead to more rapid and effective symptom relief. Additionally, the use of a sham comparator in the trial helps to rigorously test the treatment's true efficacy, adding to the excitement about its potential impact.

What evidence suggests that TMS might be an effective treatment for anorexia?

Research has shown that transcranial magnetic stimulation (TMS) can help people with anorexia nervosa. One study found that TMS improved body mass index (BMI) and reduced key symptoms of the disorder. Another study observed changes in brain blood flow related to weight changes after TMS treatment. Overall, TMS is considered safe and has shown positive results, such as reducing cravings and behaviors related to food. In this trial, participants will be assigned to either an active TMS treatment arm or a sham TMS comparator arm. These findings suggest that TMS might help change brain circuits linked to anorexia, potentially improving eating habits and body image. ^{1 2 3 4 5}

Who Is on the Research Team?

Guido Frank, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for English-speaking females aged 18 to 45 with Anorexia Nervosa as per DSM V, either restricting or binge/purge subtype. Participants must not be pregnant, have metal implants near the head, major medical illnesses, substance abuse issues in the last month, certain psychiatric disorders, abnormal blood tests results or a history of seizures among other exclusions.

Inclusion Criteria

English is primary language spoken

Restricting or binge/purge subtype

I am a woman aged between 18 and 45.

Exclusion Criteria

Permanent eye makeup or face tattoos with potential ferrous materials

Previous or current organic brain syndromes, psychotic disorders, bipolar type disorders, somatization disorders, or conversion disorder

Intracranial implant or metal object within or near the head that cannot be safely removed

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive iTBS treatment over 1 week for active group or 2 weeks for sham/active group

1-2 weeks

5 treatment days per week, 10 sessions per day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS treatment using BrainsWay Model 104 system with H1-Coil
• sham TMS using BrainsWay Model 104 system with H1-Coil

Trial Overview The study is testing Transcranial Magnetic Stimulation (TMS) using BrainsWay Model 104 system with H1-Coil to see if it can change brain activity and improve symptoms of Anorexia Nervosa. Some participants will receive real TMS while others get sham TMS without active treatment for comparison.

How Is the Trial Designed?

Group I: Active iTBS Experimental Treatment 1 Intervention

rTMS treatments will employ the Brainsway stimulator (Brainsway Ltd, Israel). Prior to the first treatment (no more than 5 days prior), each subject's motor threshold (MT) will first be determined according to published methods (Schutter, van Honk, 2006; Julkunen et al, 2009). This location, as well as the stimulation target spot, will be marked at the first session on the scalp and standard methods will be used to target this spot during treatment sessions. The modified BeamF3 scalp heuristic will be used to localize the treatment site over the left DLPFC (Mir-Moghtadaei et al., 2015). Subjects will complete 5 treatments days. A treatment day will consist of 10 treatment sessions with the start of each session timed to be at least 50 minutes from the previous session.

Group II: Sham iTBS Placebo Group 1 Intervention

The BrainsWay Model 104 with H4 coil has an integrated sham coil. The sham condition will start with the same clicking noise as the active TMS condition. Every helmet has a corresponding sham H-coil encased in the same helmet. The sham coil induces only a negligible sub-threshold field in the brain while making an identical noise and inducing some scalp sensation. Subjects will complete 5 treatments days. A treatment day will consist of 10 treatment sessions with the start of each session timed to be at least 50 minutes from the previous session. Subjects in this arm will have the option of receiving the Active iTBS protocol after they complete the 5 days of 10 daily treatment sessions.

rTMS treatment using BrainsWay Model 104 system with H1-Coil is already approved in United States, European Union for the following indications:

Approved in United States as TMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in European Union as TMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

A pilot study involving 10 right-handed individuals with anorexia nervosa showed that one session of high frequency repetitive transcranial magnetic stimulation (rTMS) was safe and well-tolerated.

After rTMS, participants reported reduced feelings of fullness, fatness, and anxiety, suggesting that rTMS may help alleviate core symptoms of anorexia nervosa and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in anorexia nervosa: a pilot study. Van den Eynde, F., Guillaume, S., Broadbent, H., et al.[2022]

In a study involving 29 participants with severe anorexia nervosa, repetitive transcranial magnetic stimulation (rTMS) was found to be an acceptable treatment, although participants noted it was time-consuming.

Post-treatment, many participants reported positive changes in their outlook and willingness to engage with their anorexia nervosa and other life aspects, suggesting rTMS may have beneficial effects beyond just physical health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'My dad was like "it's your brain, what are you doing?"': Participant experiences of repetitive transcranial magnetic stimulation treatment in severe enduring anorexia nervosa. Dalton, B., Austin, A., Ching, BCF., et al.[2022]

In a case series of five women with enduring anorexia nervosa, repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex led to significant improvements in eating disorder symptoms and mood after approximately 20 treatment sessions.

While initial improvements were noted, with some participants showing recovery at the 6-month follow-up, the benefits diminished by the 12-month follow-up, indicating the need for ongoing treatment or additional interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Enduring Anorexia Nervosa: A Case Series. McClelland, J., Kekic, M., Campbell, IC., et al.[2022]

In a pilot study involving 10 women with anorexia nervosa, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to the right dorsolateral prefrontal cortex (DLPFC) led to changes in food selection, indicating a potential therapeutic effect.

HF-rTMS was associated with increased healthiness ratings for both low- and high-fat foods and a greater selection of high-fat foods, suggesting that this stimulation may help reduce fat avoidance in individuals with anorexia nervosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study. Muratore, AF., Bershad, M., Steinglass, JE., 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]

In a follow-up study of 24 participants with severe anorexia nervosa, those who originally received real rTMS showed a medium effect size in BMI improvement after 18 months, with five achieving weight recovery compared to only one in the sham group.

Both groups experienced further improvements in eating disorder symptoms over time, indicating that while rTMS has lasting effects on mood, significant changes in BMI and symptoms may take longer to develop.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up. Dalton, B., Lewis, YD., Bartholdy, S., et al.[2021]

Anorexia nervosa patients show increased cortical excitability in both motor and esophageal areas, as evidenced by reduced resting motor thresholds and motor evoked potentials compared to healthy controls, based on a study of 13 patients and 14 matched controls.

This heightened cortical excitability correlates with clinical symptoms of anorexia, suggesting a potential mechanism underlying the disorder's pathology, although no correlation was found with depression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered cortical excitability in anorexia nervosa. Khedr, EM., El Fetoh, NA., El Bieh, E., et al.[2014]

In a study involving 26 participants with severe enduring anorexia nervosa (SE-AN), high-frequency repetitive transcranial magnetic stimulation (rTMS) led to a significant reduction in blood flow in the amygdala, which was associated with greater weight gain over 18 months.

The study suggests that changes in regional cerebral blood flow (CBF) could serve as a potential marker for treatment response to rTMS in SE-AN, highlighting the need for further research using neuroimaging to understand the neurobiological effects of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa. Dalton, B., Maloney, E., Rennalls, SJ., et al.[2021]

In a study involving two individuals with treatment-resistant anorexia nervosa, 19-20 sessions of high-frequency rTMS applied to the left dorsolateral prefrontal cortex led to improvements in eating disorder symptoms and mood.

The positive effects of rTMS were observed immediately after treatment and continued to improve at a one-month follow-up, indicating its potential as a promising adjunct treatment for anorexia nervosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvements in symptoms following neuronavigated repetitive transcranial magnetic stimulation (rTMS) in severe and enduring anorexia nervosa: findings from two case studies. McClelland, J., Bozhilova, N., Nestler, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11735571/

Efficacy of transcranial magnetic stimulation in anorexia nervosa TMS represents an effective therapy for patients with AN, leading to improvements in both BMI and core symptoms of AN, with minor and transient side effects.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9597650/

Is Repetitive Transcranial Magnetic Stimulation (RTMS) a ... The analyses show that rTMS induced large improvements in body mass index (BMI) among obese individuals. Null clinical effects have been detected for primary ...

3. jeatdisord.biomedcentral.com jeatdisord.biomedcentral.com/articles/10.1186/s40337-021-00420-w

A pilot study exploring the effect of repetitive transcranial ... This exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight.

4. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp-rj.2023.180302

Repetitive Transcranial Magnetic Stimulation Strategies in ... Findings indicated that rTMS is safe for patients with anorexia nervosa and well tolerated, but large randomized controlled trials comparing ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178117319960

Repetitive transcranial magnetic stimulation in the ... In this review, some studies showed relatively positive results with safe outcomes and with reduction of both craving and eating behaviors with active ...