Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

NCT06138782 | Active Not Recruiting FDA Device

• 1 other identifier: 23-39333
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Transcranial Magnetic Stimulation (TMS) is approved by the Food and Drug Administration (FDA) for the treatment of refractory Major Depressive Disorder (MDD) and obsessive-compulsive disorder (OCD). Anorexia nervosa (AN) is characterized by restrictive eating leading to low weight and associated complications. There is an emerging understanding that the symptoms of OCD and AN overlap as AN can be characterized by obsessive thought patterns around food and compulsive restricting and weight loss behaviors. Both conditions are characterized by a propensity toward cognitive inflexibility and the conditions may share neural substrates that maintain maladaptive habitual behaviors and cognitive rigidity. An evidence-based repetitive transcranial magnetic stimulation (rTMS) target for OCD is the orbitofrontal cortex (OFC). The investigators intend to determine if the OFC is also a potential rTMS target for AN and to determine if there is a characteristic pattern of functional network reorganization as characterized by functional magnetic resonance imaging (fMRI) in TMS responders.

Conditions

Anorexia Nervosa

Keywords

anorexia; AN; anorexia nervosa; OCD; obsessive; obsessive-compulsive disorder

Outcome Measures

Primary Outcomes (1)

• Eating Disorders Examination - Questionnaire (EDE-Q)

  The Eating Disorder Examination Questionnaire (EDE-Q) is a 28-item self-report questionnaire designed to assess the range, frequency and severity of behaviours associated with a diagnosis of an eating disorder. It is categorised into 4 subscales (Restraint, Eating Concern, Shape Concern and Weight Concern) and an overall global score, with a higher score indicating more problematic eating difficulties.

  Baseline; day 1, 5, & 10 of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

Secondary Outcomes (8)

• Yale Brown Obsessive Compulsive Scale (Y-BOCS)

  Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

• Compulsive Exercise Test (CET)

  Baseline; day 1, 5, & 10 of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

• State Trait Anxiety Index (STAI)

  Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

• Ecological Momentary Assessment (EMA)

  Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).

Study Arms (1)

TMS (Aim 2)

EXPERIMENTAL

Our protocol consists of five treatments of inhibitory continuous TBS (cTBS) to the R OFC lasting three minutes delivered every hour over the course of 10 days (2 weeks) for a total of 50 treatments.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Our protocol consists of five treatments of inhibitory continuous TBS (cTBS) to the R OFC lasting three minutes delivered every hour over the course of 10 days (2 weeks) for a total of 50 treatments.

TMS (Aim 2)

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• outpatients
• ages 16 - 75 for Aim 2
• meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN
• stable on chronic psychotropic medications for 4 weeks prior to the study and agreeable to continue throughout the study
• participants may continue to take medications and record daily usage throughout the study
• capacity to provide informed consent
• ability to tolerate clinical study procedures
• successfully complete the screening forms without any contraindications

You may not qualify if:

• Psychiatric: schizophrenia, bipolar disorder, prior psychosurgery, prior electroconvulsive therapy (ECT)
• Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, hydrocephalus, sequelae of meningitis)
• TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics; medications or systemic illness that predispose seizure risk
• Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension)
• Females who are pregnant or nursing
• Inability to complete the research study

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94107, United States

Location

Related Publications (10)

• Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):931-938. doi: 10.1176/appi.ajp.2019.18101180. Epub 2019 May 21.

  PMID: 31109199 BACKGROUND

• Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. doi: 10.1016/s0896-6273(00)00113-6. No abstract available.

  PMID: 11144344 BACKGROUND

• Kaye W. Is food restriction in anorexia nervosa caused by reduced reward and/or increased inhibition? Neuropsychopharmacology. 2011;36(Kaye W.) UCSD, Department of Psychiatry, San Diego, United States):S48. doi:10.1038/npp.2011.290

  BACKGROUND

• Kaye WH, Bulik CM. Treatment of Patients With Anorexia Nervosa in the US-A Crisis in Care. JAMA Psychiatry. 2021 Jun 1;78(6):591-592. doi: 10.1001/jamapsychiatry.2020.4796. No abstract available.

  PMID: 33625500 BACKGROUND

• Murray SB, Strober M, Craske MG, Griffiths S, Levinson CA, Strigo IA. Fear as a translational mechanism in the psychopathology of anorexia nervosa. Neurosci Biobehav Rev. 2018 Dec;95:383-395. doi: 10.1016/j.neubiorev.2018.10.013. Epub 2018 Oct 28.

  PMID: 30392878 BACKGROUND

• Nauczyciel C, Le Jeune F, Naudet F, Douabin S, Esquevin A, Verin M, Dondaine T, Robert G, Drapier D, Millet B. Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study. Transl Psychiatry. 2014 Sep 9;4(9):e436. doi: 10.1038/tp.2014.62.

  PMID: 25203167 BACKGROUND

• Posner J, Song I, Lee S, Rodriguez CI, Moore H, Marsh R, Blair Simpson H. Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder. Hum Brain Mapp. 2017 Feb;38(2):678-687. doi: 10.1002/hbm.23408. Epub 2016 Sep 23.

  PMID: 27659299 BACKGROUND

• Steward T, Menchon JM, Jimenez-Murcia S, Soriano-Mas C, Fernandez-Aranda F. Neural Network Alterations Across Eating Disorders: A Narrative Review of fMRI Studies. Curr Neuropharmacol. 2018;16(8):1150-1163. doi: 10.2174/1570159X15666171017111532.

  PMID: 29046154 BACKGROUND

• Walsh BT, Xu T, Wang Y, Attia E, Kaplan AS. Time Course of Relapse Following Acute Treatment for Anorexia Nervosa. Am J Psychiatry. 2021 Sep 1;178(9):848-853. doi: 10.1176/appi.ajp.2021.21010026. Epub 2021 Jun 22.

  PMID: 34154394 BACKGROUND

• Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol. 2012;8:49-76. doi: 10.1146/annurev-clinpsy-032511-143049. Epub 2012 Jan 6.

  PMID: 22224834 BACKGROUND

MeSH Terms

Conditions

Anorexia Nervosa; Anorexia; Obsessive-Compulsive Disorder

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anxiety Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Andrew M Lee, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: November 18, 2023
• Study Start: October 16, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)