Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT06138782

Collaborator

(none)

Enrollment

Location

Arm

22.5

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa	Device: Repetitive Transcranial Magnetic Stimulation (rTMS)	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

Actual Study Start Date :

Oct 16, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMS (Aim 2) 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) 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.

Arm

Intervention/Treatment

Experimental: TMS (Aim 2)

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)

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.

Outcome Measures

Primary Outcome Measures

Eating Disorders Examination - Questionnaire (EDE-Q) [Baseline; day 1, 5, & 10 of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).]
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.

Secondary Outcome Measures

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).]
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.
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).]
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.
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).]
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.
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).]
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.
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).]
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.
Hamilton Self-Rating Scale for Depression (HAM-D) [Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).]
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.
Intolerance of Uncertainty Scale - short form (IUS-12) [Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).]
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.
Repetitive Thinking Questionnaire-10 (RTQ-10) [Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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