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| Name | Class |
|---|---|
| University of Minnesota | OTHER |
| Butler Hospital | OTHER |
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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:
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, inhibitory theta burst stimulation (iTBS) to the dorsolateral prefrontal cortext (dlPFC), or continuous theta burst stimulation (cTBS) to the presupplementary motor area (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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ERP+iTBS | Experimental | 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). |
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| ERP+cTBS | Experimental | 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). |
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| ERP+Sham | Active Comparator | Participants will receive two weeks (10 sessions) of sham ("fake") TMS, followed immediately by Exposure Plus Response Prevention (ERP). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation: intermittent theta burst to dorsolateral prefrontal cortex | Device | TMS will be delivered over the dorsolateral prefrontal cortex (dlPFC) using an intermittent bursting pattern |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristen Benito, PhD | Emma Pendleton Bradley Hospital | Principal Investigator |
| Christine Conelea, PhD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55414 | United States | ||
| Emma Pendleton Bradley Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39696590 | Derived | Conelea C, Breitenfeldt C, Wilens A, Carpenter L, Greenberg B, Herren J, Jacob S, Lewis C, McLaughlin N, Mueller BA, Nelson S, O'Connor E, Righi G, Widge AS, Fiecas M, Benito K. The NExT trial: Protocol for a two-phase randomized controlled trial testing transcranial magnetic stimulation to augment exposure therapy for youth with OCD. Trials. 2024 Dec 18;25(1):835. doi: 10.1186/s13063-024-08629-1. |
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| ID | Type | URL | Comment |
|---|---|---|---|
| Individual Participant Data Set | View IPD |
We will share all de-identifiable data from study measures through the National Institute of Mental Health (NIMH) Data Archive (NDA) using the data dictionaries available in NDA. As per NIMH Data Archive, data will be deidentified and assigned a Global Unique Identifier (GUID). We will also share deidentified study data via the National Database for Clinical Trials (NDCT) related to Mental Illness.
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We will upload raw data twice yearly and all other data at the time of publication or end of the project. The research community will have access to all de-identifiable data when the award ends. NDA will make decisions about how long to preserve the data. We will share the study protocol and consent form after obtaining IRB approval.
Data can be accessed through the NDA by investigators working under an institution with a Federal Wide Assurance (FWA)
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Quadruple-masked Randomized Controlled Trial (RCT) with parallel assignment
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Participants, parents (if applicable), the ERP therapist, the independent evaluator (but not active vs. sham status).
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| Exposure with Response Prevention | Behavioral | ERP will be delivered daily, immediately following TMS |
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| Transcranial Magnetic Stimulation: Sham | Device | 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 |
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| Transcranial Magnetic Stimulation: continuous theta burst to pre supplementary motor area | Device | TMS will be delivered over the pre supplementary motor area (preSMA) using a continuous bursting pattern |
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| Riverside |
| Rhode Island |
| 02915 |
| United States |
| ID | Term |
|---|---|
| D009771 | Obsessive-Compulsive Disorder |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D004561 | Transcutaneous Electric Nerve Stimulation |
| D007171 | Implosive Therapy |
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D012046 | Rehabilitation |
| D000698 | Analgesia |
| D000760 | Anesthesia and Analgesia |
| D003887 | Desensitization, Psychologic |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
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