rTMS for Anorexia Nervosa

(FED Trial)

Overseen By Kayla D Stone, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Mania, Psychosis, Autism, 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: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for adolescents with anorexia nervosa who haven't responded well to Family Based Treatment (FBT). It uses repetitive transcranial magnetic stimulation (rTMS), targeting specific brain areas linked to anxiety, to assess its impact on treatment outcomes. Participants will receive either active rTMS or a placebo (an inactive treatment that looks and sounds the same) to compare effects. Suitable candidates have been diagnosed with anorexia nervosa, are medically stable, and have no plans to move for several months. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from an innovative treatment approach.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as the dose has been stable for six weeks before the trial and you agree not to change the medication or dosage during the trial period.

What prior data suggests that rTMS is safe for adolescents with anorexia nervosa?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated for people with anorexia nervosa. Studies have found that patients usually experience few side effects, which are mostly mild. Common side effects might include a slight headache or scalp discomfort, but these are temporary. Importantly, no serious side effects have been reported with rTMS for anorexia. This treatment has also been used safely for other conditions like anxiety and depression, supporting its safety. Overall, evidence suggests that rTMS is a safe option for those considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about repetitive transcranial magnetic stimulation (rTMS) for anorexia nervosa because it offers a novel approach by using magnetic fields to stimulate specific areas of the brain, potentially impacting neural circuits involved in appetite and mood regulation. Unlike standard treatments that might focus on psychotherapy or medication to address symptoms, rTMS directly targets the dorsolateral prefrontal cortex (DLPFC), which is thought to be involved in the cognitive control of eating behavior. This non-invasive technique could present a new avenue for treatment, especially for patients who have not responded well to existing therapies. Additionally, the use of rTMS might offer fewer side effects compared to pharmacological options, making it an attractive alternative for long-term management.

What evidence suggests that rTMS could be an effective treatment for anorexia nervosa?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can aid individuals with anorexia nervosa (AN) by improving body weight and reducing key symptoms of the disorder. Studies have found that rTMS is safe and generally well-tolerated, with only minor side effects. In this trial, participants will receive either active rTMS or sham rTMS. The active treatment targets specific brain areas, such as the right dorsolateral prefrontal cortex, which is linked to reducing anxiety. Since anxiety can hinder the treatment of AN, rTMS might enhance the effectiveness of traditional treatments like Family Based Treatment (FBT) for teenagers with AN by helping to manage anxiety. ^{1 2 3 5 6}

Who Is on the Research Team?

Frank P MacMaster, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adolescents aged 12 to 18 with Anorexia Nervosa, as confirmed by medical and psychiatric assessment. Participants must be medically stable, fluent in English, and on a steady dose of any AN or psychiatric medications for six weeks prior without plans to change during the study.

Inclusion Criteria

English fluency (i.e., able to consent and assent to the study)

My health condition is currently stable.

My medication for AN or psychiatric conditions has been stable for 6 weeks, and I won't change it during the trial.

Exclusion Criteria

I have been diagnosed with post-concussive syndrome.

I plan to be available for clinic visits for at least 6-9 months after starting treatment.

I have been diagnosed with mania or psychosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Family Based Treatment (FBT) Phase 1

Participants undergo Family Based Treatment (FBT) focusing on parental involvement to address disordered eating and achieve healthy body weight

4 weeks

Weekly visits

Repetitive Transcranial Magnetic Stimulation (rTMS)

Participants receive rTMS targeting the right dorsolateral prefrontal cortex to reduce anxiety and facilitate response to FBT

4 weeks

20 visits (weekdays)

Follow-up

Participants are monitored for changes in anxiety and weight restoration after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The trial tests if Repetitive Transcranial Magnetic Stimulation (rTMS) can improve outcomes in Family Based Treatment (FBT) for anorexia by targeting brain areas related to anxiety. It focuses on whether stimulating the right DLPFC enhances FBT effectiveness.

How Is the Trial Designed?

Group I: Active Repetitive Transcranial Magnetic Stimulation Experimental Treatment 1 Intervention

rTMS parameters are intensity 110% resting motor threshold (RMT), frequency 1Hz, duration = 30 minutes (1800 stimulations), targeting the right DLPFC. To target the dorsolateral prefrontal cortex (DLPFC) for rTMS treatment we will use the traditional method (i.e. the 5cm rule; George et al., 1995, 1996; Herwig et al., 2001, 2003; MacMaster et al., 2019), in which the TMS coil is placed 5 cm anterior to the participant's motor cortex along a line to the nasion. Treatments will occur on weekdays at the same time of day for 4 weeks (20 total).

Group II: Sham Repetitive Transcranial Magnetic Stimulation Placebo Group 1 Intervention

For the sham rTMS group, a sham coil is used: this sham method does not emit any magnetic field, and therefor does not affect brain activity, but it does produce auditory sensations that is indistinguishable from active rTMS in naïve subjects

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

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]

This feasibility randomized controlled trial will assess the effects of real versus sham repetitive transcranial magnetic stimulation (rTMS) in 44 adults with severe and enduring anorexia nervosa (SEED-AN), aiming to gather preliminary efficacy data and inform future large-scale studies.

The trial will evaluate a wide range of outcomes, including weight, eating disorder symptoms, quality of life, and neuroimaging measures, to determine the acceptability and tolerability of rTMS as a treatment for SEED-AN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial. Bartholdy, S., McClelland, J., Kekic, M., et al.[2022]

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 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]

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 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]

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. 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 ...

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

A pilot study exploring the effect of repetitive transcranial ... Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN).

4. 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 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04409704

Repetitive Transcranial Magnetic Stimulation of the ... This project proposes to perform a pilot study of fMRI targeted Dorsomedial Prefrontal Cortex repetitive transcranial magnetic stimulation (DMPFC-rTMS) on ...