Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

Anorexia Nervosa Clinical Trial

Official title:

Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06138782
• Other study ID #: 23-39333
• Status: Recruiting
• Phase: N/A
• Start date: October 16, 2023
• Est. completion date: September 2025

Study information

• Verified date: November 2023
• Source: University of California, San Francisco
• Contact: Andrew M Lee, MD, PhD
• Phone: 415-476-7000
• Email: AndrewMoses.Lee[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

To determine if accelerated theta burst rTMS can treat symptoms of AN and normalize abnormal network connectivity, the investigators will enroll 20 patients with AN (aged 18-45) to receive five treatments of inhibitory continuous theta burst rTMS to the right orbitofrontal cortex (R OFC) lasting three minutes delivered every hour over the course of 10 days (2 weeks) for a total of 50 treatments, with follow-up immediately post-treatment, and at 1 month. Clinical symptom change will be determined with weight gain from percent expected body weight (%EBW) and clinical interview with the Eating Disorders Examination (EDE) as well as validated self-report. For Hypothesis 1: At 1-month post-rTMS, the investigators expect increased %EBW, and meaningful reductions in AN compulsive symptoms per the EDE. For Hypothesis 2: The investigators intend to identify changes in the default mode network comparing before and after TMS that are associated with an improvement in AN compulsive symptoms.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• outpatients

• ages 18 - 45 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation (rTMS)
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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yale Brown Obsessive Compulsive Scale (Y-BOCS)	The Y-BOCS is a 10-item ordinal scale (0-4) that rates the severity separately for both obsessions and compulsions of OCD according to the time occupied, degree of interference, subjective distress, internal resistance, and degree of control. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Compulsive Exercise Test (CET)	The CET is a 24-item self-report measure designed to assess the core features of excessive exercise in the eating disorders. Higher scores indicate worse outcome.	Baseline; day 1, 5, & 10 of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	State Trait Anxiety Index (STAI)	The Spielberger State-Trait Anxiety Inventory (STAI) is a 40-item self-report measure of anxiety using a 4-point Likert-type scale (from 0 to 3 points) for each item. It has two scales: State anxiety, i.e. how one feels at the moment; and Trait anxiety, i.e. how one generally feels. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Ecological Momentary Assessment (EMA)	Ecological momentary assessments (EMAs) study people's thoughts and behavior in their daily lives by repeatedly collecting data in an individual's normal environment, at or close to the time that the individual carries out that behavior. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS)	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Hamilton Self-Rating Scale for Depression (HAM-D)	The HAM-D is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Intolerance of Uncertainty Scale - short form (IUS-12)	The Intolerance of Uncertainty Scale (IUS) includes items relating to the idea that uncertainty is unacceptable, reflects badly on a person, and leads to frustration, stress, and the inability to take action. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Secondary	Repetitive Thinking Questionnaire-10 (RTQ-10)	The Repetitive Thinking Questionnaire (RTQ) was developed by combining items from commonly used measures of worry, rumination, and post-event processing, and then modifying the items to remove diagnosis-specific content. It is used to measure repetitive negative thinking. Higher scores indicate worse outcome.	Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).