Transcranial Magnetic Stimulation (TMS) in the Treatment of Anorexia Nervosa

Anorexia Nervosa Clinical Trial

Official title:

Harnessing Neurostimulation to Improve Treatment Outcome in Anorexia Nervosa

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05368844
• Other study ID #: 202030
• Status: Recruiting
• Phase: N/A
• Start date: June 16, 2022
• Est. completion date: May 1, 2025

Study information

• Verified date: June 2024
• Source: University of California, San Diego
• Contact: Megan Shott, BS
• Phone: 858-246-5272
• Email: mshott[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The goals for this study are 1) to test the feasibility of iTBS in AN and 2) to gather pilot data to as proof of concept of its effectiveness in AN prior to applying for larger funding to the NIH.

Subjects will complete a battery of self-assessments and a diagnostic assessment in order to determine eligibility and for characterization of behavior to be used in later analyses. After eligibility is confirmed, subjects will take part in iTBS treatment over either 1 week (active iTBS groups) or 2 weeks, (1 week sham treatment group, followed by 1 week active iTBS).

The design will be a randomized control design that also includes a cross over design. Subjects will be randomized to either Group 1, Active iTBS, or Group 2, Sham/Active iTBS.

Group 1 will receive active iTBS over 5 days, with 10 brief sessions per day (5 study days/50 session total). Group 2 will receive Sham over 5 days, with 10 brief sessions per day, and this will be followed by active iTBS over 5 days, with 10 brief sessions per day (20 study days/100 session total).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Females ages 18 to 45 years

• Diagnostic criteria. Current diagnosis of AN according to the DSM V, including having a severe fear of weight gain and body image distortion

• Restricting or binge/purge subtype

• English is primary language spoken

Exclusion Criteria:

• Subjects who are pregnant or think they may be pregnant will be excluded from the study.

• Subjects will not have electrolyte, blood count or kidney or liver function abnormalities. Prior to starting the TMS treatment (Visit 2), all subjects will complete a basic metabolic panel (must be completed within no more than one week prior to the start of the TMS treatment) to rule out electrolyte or metabolic abnormalities.

• Subjects may not have a lifetime history of a condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy or single seizure related to a known drug related event.

• Subjects may not have a history of significant head trauma with loss of consciousness for greater than 5 minutes.

• Subjects may not have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.

• Subjects may not currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit TMS efficacy or have a history of lack of response to accelerated course of iTBS or rTMS in the past.

• Subjects may not have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump.

• Subjects may not have symptoms of alcohol or substance abuse or dependence in the past month, may not have previous or current organic brain syndromes, psychotic disorders, bipolar type disorders, somatization disorders, or conversion disorder.

• Antidepressant bupropion or other seizure threshold lowering medication or are currently taking tricyclic antidepressants or neuroleptics.

• Permanent eye makeup (such as eyeliner or eyebrows) or other face tattoos due to potential ferrous materials used in the tattoo ink

• Subjects may not have a history of neurocardiogenic syncope as there is an increased risk of TMS-induced neurocardiogenic syncope in adolescent populations.

• Subjects may not have implanted neurostimulators, intracardiac lines, or heart disease that causes moderate to severe symptoms and/or is characterized by moderate to severe pathology (including a recent history of myocardial infarction and heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV).

• Subjects may not have a history of stroke or other brain lesions.

• Subjects may not have a history of suicide attempt(s).

• Subject may not have a family history of epilepsy.

• Cannot refrain from drinking alcohol for the duration of the study. Subjects will be asked to refrain from consuming alcohol for the duration of the study. At the beginning of each treatment day subjects will be asked about alcohol consumption in the last 48 hours and will not complete the treatment sessions that day if they have had alcohol in the last 48 hours.

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

Device:
• rTMS treatment using BrainsWay Model 104 system with H1-Coil
5 days of 10 daily sessions of rTMS treatment
• sham TMS using BrainsWay Model 104 system with H1-Coil
5 days of 10 daily sessions of sham iTBS treatment

Locations

Country	Name	City	State
United States	University of California San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (4)

Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7. — View Citation

Frank GKW, DeGuzman MC, Shott ME. Motivation to eat and not to eat - The psycho-biological conflict in anorexia nervosa. Physiol Behav. 2019 Jul 1;206:185-190. doi: 10.1016/j.physbeh.2019.04.007. Epub 2019 Apr 10. — View Citation

Mir-Moghtadaei A, Caballero R, Fried P, Fox MD, Lee K, Giacobbe P, Daskalakis ZJ, Blumberger DM, Downar J. Concordance Between BeamF3 and MRI-neuronavigated Target Sites for Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex. Brain Stimul. 2015 Sep-Oct;8(5):965-73. doi: 10.1016/j.brs.2015.05.008. Epub 2015 May 29. — View Citation

Schutter DJ, van Honk J. A standardized motor threshold estimation procedure for transcranial magnetic stimulation research. J ECT. 2006 Sep;22(3):176-8. doi: 10.1097/01.yct.0000235924.60364.27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of TMS sessions	To establish feasibility of iTBS in anorexia nervosa the investigator will assess the following: total percent of sessions completed by the subject.	at study completion, up to 2 weeks
Primary	Acceptability of TMS procedures	To establish acceptability of iTBS in anorexia nervosa the investigator will assess the following: subjects will be asked open-ended questions about the subject's experience of the study.	at study completion, up to 2 weeks
Secondary	Eating Disorders Inventory 3 Drive for Thinness Subscale	The Eating Disorders Inventory 3 is a self report assessment that measures core eating disorder symptoms. Subjects will complete this measure at the beginning and end of the study and the investigator will measure the change in scores. The Drive for Thinness Subscale has a range of 0 to 28 where higher scores mean worse outcome.	Change from baseline to study completion, up to 2 weeks
Secondary	Eating Disorders Inventory 3 (EDI-3) Body Dissatisfaction Subscale	The Eating Disorders Inventory 3 is a self report assessment that measures core eating disorder symptoms. Subjects will complete this measure at the beginning and end of the study and the investigator will measure the change in scores. The Drive for Thinness Subscale has a range of 0 to 40 where higher scores mean worse outcome.	Change from baseline to study completion, up to 2 weeks
Secondary	Weight gain	Body Mass Index over time as a measure of food intake from the start to end of the study.	Change in body mass index from baseline to study completion, up to 2 weeks
Secondary	Spielberger State-Trait Anxiety Scale-Version Y (STAI-Y) State Anxiety Subscale	The Spielberger State-Trait Anxiety Scale-Version Y is a self report assessment that measure state and trait anxiety. Subjects will complete this measure at the beginning and end of the study and the investigator will measure the change in scores of State Anxiety. State anxiety has a range of 0 to 80 with higher scores indicating worse outcome.	Change from baseline to study completion, up to 2 weeks
Secondary	Spielberger State-Trait Anxiety Scale-Version Y (STAI-Y) Trait Anxiety Subscale	The Spielberger State-Trait Anxiety Scale-Version Y is a self report assessment that measure state and trait anxiety. Subjects will complete this measure at the beginning and end of the study and the investigator will measure the change in scores of Trait Anxiety. Trait anxiety has a range of 0 to 80 with higher scores indicating worse outcome.	Change from baseline to study completion, up to 2 weeks
Secondary	Beck Depression Inventory	The Beck Depression Inventory is a self report assessment that measures depression. Subjects will complete this measure at the beginning and end of the study and the investigator will measure the change in scores. The score range is from 0 to 63 with higher scores indicating worse outcome.	Change from baseline to study completion, up to 2 weeks