TMS + Exposure Therapy for Pediatric OCD

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare different forms of transcranial magnetic stimulation (TMS) for improving the outcomes of Exposure with Response Prevention (ERP) in youth and young adults with Obsessive-Compulsive Disorder (OCD). Researchers will compare three groups: ERP with one of two different active (real) forms of TMS vs. ERP with sham (fake) TMS. The main questions this study aims to answer are: 1) whether TMS normalizes functioning in brain circuits that contribute to compulsive behavior, and 2) whether TMS reduces compulsions during ERP. Participants will: Complete clinical interviews, questionnaires, and computerized tasks Complete two MRIs (brain scans) Receive daily TMS followed by ERP for two weeks (10 sessions)

Detailed Description
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Pediatric OCD is a public health problem and many remain symptomatic even after receiving efficacious treatments. The success of exposure and response prevention (ERP), a first-line behavioral treatment, depends on the ability to refrain from compulsions during exposure tasks. Improving this therapy critical behavior is a potentially important strategy for ERP augmentation. Repetitive transcranial magnetic stimulation (rTMS) can be leveraged to stimulate healthier functioning of brain circuits underlying therapy critical behaviors. The overall objective of this project is to test whether augmenting ERP with rTMS over cortical nodes of select cortico-striatal circuits implicated in compulsivity can normalize connectivity and enhance response prevention in youth and young adults with OCD. This project will use a masked RCT design to test whether ERP+TMS engages 1) hypothesized circuits involved in compulsivity and 2) observed response prevention during ERP exposure tasks. Youth ages 12-21 years with OCD will complete a full course of ERP plus randomly assigned TMS regimens of sham, iTBS to dlPFC, or cTBS to pSMA (n=20 per group). Milestones for the R61 phase are determination that at least one active rTMS condition a) changes resting state functional connectivity in the hypothesized circuit within- and between-subjects and b) is safe and feasible.

Official Title
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Transcranial Magnetic Stimulation to Augment Exposure and Response Prevention for Pediatric OCD

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation: intermittent theta burst to dorsolateral prefrontal cortex
* Behavioral: Exposure with Response Prevention
* Device: Transcranial Magnetic Stimulation: Sham
* Device: Transcranial Magnetic Stimulation: continuous theta burst to pre supplementary motor area


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 12 and 21 years. Presence of OCD, as indicated by a score of > 16 on the Children's Yale-Brown Obsessive Compulsive Scale, indicating moderate or greater OCD symptoms. Presence of motor compulsions on CY-BOCS compulsion checklist English fluency to ensure comprehension of informed consent and study measures and instructions. Exclusion Criteria: Decline to provide informed consent. Medical conditions contraindicated or associated with altered TMS risk profile, including: History of intracranial pathology, epilepsy or seizure disorders, traumatic brain injury, brain tumor, stroke, implanted medical devices or metallic objects in the head, current pregnancy or girls of childbearing age not using effective contraception, or any other serious medical condition. Inability to undergo MRI. Left handedness. Active suicidality. Previous diagnosis of psychosis or cognitive disability. Substance abuse or dependence within the past year. Concurrent psychotherapy focused on OCD. Concurrent TMS or receipt of any TMS experimental or clinical treatment less than 3 months prior to enrollment. Taking a medication deemed to pose increased seizure risk per physician review Taking a medication that has not reached stability criterion (same medication and dose for 6 weeks with no planned changes over the study period)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Quadruple-masked Randomized Controlled Trial (RCT) with parallel assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ERP+iTBS<br>Participants will receive two weeks (10 sessions) of intermittent theta burst stimulation (iTBS; a form of TMS) targeting the dorsolateral prefrontal cortex (dlPFC), followed immediately by Exposure Plus Response Prevention (ERP). | Device: Transcranial Magnetic Stimulation: intermittent theta burst to dorsolateral prefrontal cortex<br>* TMS will be delivered over the dorsolateral prefrontal cortex (dlPFC) using an intermittent bursting pattern<br>* Other names: iTBS;Behavioral: Exposure with Response Prevention<br>* ERP will be delivered daily, immediately following TMS<br>* Other names: CBT;|
| Experimental: ERP+cTBS<br>Participants will receive two weeks (10 sessions) of continuous theta burst stimulation (cTBS; a form of TMS) targeting the presupplementary motor area (pSMA), followed immediately by Exposure Plus Response Prevention (ERP). | Behavioral: Exposure with Response Prevention<br>* ERP will be delivered daily, immediately following TMS<br>* Other names: CBT;Device: Transcranial Magnetic Stimulation: continuous theta burst to pre supplementary motor area<br>* TMS will be delivered over the pre supplementary motor area (preSMA) using a continuous bursting pattern<br>* Other names: Neuromodulation;|
| Active Comparator: ERP+Sham<br>Participants will receive two weeks (10 sessions) of sham (fake) TMS, followed immediately by Exposure Plus Response Prevention (ERP). | Behavioral: Exposure with Response Prevention<br>* ERP will be delivered daily, immediately following TMS<br>* Other names: CBT;Device: Transcranial Magnetic Stimulation: Sham<br>* Sham stimulation will use the Magstim sham air-cooled coil, which produces auditory signals and appears identical to an active coil but contains a mu-metal shield that diverts the majority of the magnetic flux such that a minimal (<3%) magnetic field is delivered to the cortex<br>* Other names: Neuromodulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Magnetic Resonance Imaging (fMRI): connectivity of the pSMA-DLS circuit | z-score representing change in resting state connectivity between presupplementary motor area (pSMA) and dorsolateral striatum (DLS) | change from baseline at two weeks (post-treatment) | 
| Functional Magnetic Resonance Imaging (fMRI): connectivity of the dlPFC-DMS circuit | z-score representing change in resting connectivity between dorsolateral prefrontal cortex and dorsomedial striatum (DMS) | change from baseline at two weeks | 
| Observed Compulsive Behavior | Mean proportion of time during which compulsions are observed during ERP sessions | two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child/Adult Yale-Brown Obsessive Compulsive Inventory | Independent-Evaluator (IE) rated measure of OCD symptom severity. Rated on 0 (no symptoms) to 40 (most extreme symptoms) scale | change from baseline at two weeks (post-treatment) |