Clinical trial NCT06138782: Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation
Official title: Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anorexia Nervosa
Keywords: anorexia
AN
anorexia nervosa
OCD
obsessive
obsessive-compulsive disorder
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 16-45) 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.

Eligibility criteria: Inclusion Criteria:

* 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

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

Primary outcomes:
measure: Eating Disorders Examination - Questionnaire (EDE-Q)
timeFrame: 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:
measure: Yale Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Compulsive Exercise Test (CET)
timeFrame: Baseline; day 1, 5, & 10 of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: State Trait Anxiety Index (STAI)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Ecological Momentary Assessment (EMA)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Hamilton Self-Rating Scale for Depression (HAM-D)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Intolerance of Uncertainty Scale - short form (IUS-12)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
measure: Repetitive Thinking Questionnaire-10 (RTQ-10)
timeFrame: Baseline; all 10 days of TMS; every follow-up (weeks 1, 2, & 3 after final TMS treatment; every month for a year).
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Andrew M Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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