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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Anorexia nervosa is a severe psychiatric disorder associated with food avoidance and body image distortion, that is feeling fat despite being underweight. It is the third most common chronic illness among adolescent females, and its mortality reaches its peak between the ages 16 and 29 years old. There are very few treatments for anorexia nervosa and especially no biological treatments have been approved. Recent brain imaging research has repeatedly implicated brain circuits that include the insula in the disorder. The insula is a brain region important in taste processing as well as in the integration of body perception and has strong connections to the brain reward system. Transcranial magnetic stimulation (TMS) is a relatively new methodology that has been shown to alter neurocircuitry and alleviate depression. Here, the study goal is to develop TMS as a methodology to change altered neurocircuitry in anorexia nervosa and alleviate disorder specific behaviors.

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 data supports the effectiveness of this treatment for anorexia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can lead to improvements in symptoms for individuals with severe and enduring anorexia nervosa. Studies have found changes in food choice behavior and cerebral blood flow, suggesting potential benefits of rTMS in treating anorexia. ^{1 2 3 4 5}

Is TMS safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated in humans, with most studies reporting a reassuring safety profile, even when used for conditions like obesity and anorexia nervosa. ^{2 3 6 7 8}

How is rTMS treatment for anorexia different from other treatments?

rTMS (repetitive transcranial magnetic stimulation) is unique because it targets specific brain areas, like the dorsolateral prefrontal cortex, to modulate neural activity, which is different from traditional therapies that focus on psychological or nutritional interventions. This brain-directed approach is novel for anorexia, especially for those who have not responded to other treatments. ^{1 2 3 5 9}

Research Team

Guido Frank, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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 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]

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]

References

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

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Enduring Anorexia Nervosa: A Case Series. [2022]

2. United States 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. [2022]

3. England 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. [2018]

4. England 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up. [2021]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in anorexia nervosa: a pilot study. [2022]

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

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

9. France pubmed.ncbi.nlm.nih.gov

Altered cortical excitability in anorexia nervosa. [2014]