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The goal of this clinical trial is to learn whether brain scan results can help predict and track changes in obsessive-compulsive disorder, or OCD, symptoms in children and teens ages 10 to 17 who receive Exposure and Response Prevention therapy, also called ERP. ERP is a type of therapy in which participants practice facing OCD-related fears while resisting rituals or compulsions.
The main question this study aims to answer is:
Can each participant's pattern of brain connections, measured with functional MRI brain scans, help predict and track weekly changes in OCD symptoms during and after a 14-week course of ERP, including during planned monthly booster sessions and additional booster sessions offered if symptoms worsen?
All participants will receive ERP. There is no placebo and no comparison group.
Participants will:
This study examines whether individualized brain-connectivity measures obtained with repeated functional magnetic resonance imaging can help predict and track symptom change during exposure and response prevention, an evidence-based cognitive-behavioral therapy for pediatric obsessive-compulsive disorder.
OCD is characterized by obsessions, compulsions, or both, and in youth it can substantially interfere with school, family life, social development, and daily functioning. Although ERP and serotonin reuptake inhibitor medications are standard treatments for pediatric OCD, clinical outcomes vary. Some youth respond robustly, while others have partial improvement, persistent residual symptoms, or symptom recurrence after initial gains. Current clinical practice lacks individualized biological markers that can track treatment response over time or help identify which patients may require more intensive or alternative intervention strategies.
The scientific rationale for this study is that OCD symptoms have been linked to dysfunction in cortico-striato-thalamo-cortical brain circuits, including orbitofrontal cortex and striatal regions. However, these circuits vary across individuals, and group-average neuroimaging findings have not yet yielded clinically useful biomarkers for individual patients. Precision functional mapping uses repeated fMRI scans from the same person to generate individualized estimates of functional brain networks. By pairing ERP with longitudinal clinical assessment and repeated neuroimaging, this study will evaluate whether participant-specific functional connectivity features, particularly resting-state functional connectivity between orbitofrontal cortex and ventral striatum, are associated with changes in OCD symptom severity over time.
The broader anticipated benefit is scientific: the study may help clarify how individualized brain-connectivity patterns change during ERP and how those changes relate to symptom trajectory, treatment response, and maintenance or recurrence of symptoms. Findings may inform future approaches to personalized pediatric OCD care, including earlier identification of youth who may benefit from treatment augmentation or alternative strategies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exposure and Response Prevention Therapy | Experimental | Participants receive exposure and response prevention (ERP) therapy, an evidence-based form of cognitive behavioral therapy for obsessive-compulsive disorder. Participants also receive repeated clinical assessments and research MRI sessions. ERP consists of 14 weekly sessions of approximately 60 minutes each, followed by three scheduled monthly booster sessions and optional symptom-triggered booster sessions during the maintenance phase. ERP may be delivered in person or by HIPAA-compliant telehealth. Clinical assessments are used to measure OCD symptoms and related outcomes over time, and MRI sessions are used to evaluate brain connectivity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exposure and Response Prevention Therapy | Behavioral | Exposure and response prevention (ERP) is an evidence-based form of cognitive behavioral therapy for obsessive-compulsive disorder. ERP involves graded exposure to obsession-triggering cues while supporting participants in refraining from compulsive responses. In this study, participants receive 14 planned weekly ERP sessions of approximately 60 minutes each, followed by three scheduled monthly booster sessions and optional symptom-triggered booster sessions during the maintenance phase. ERP may be delivered in person or by HIPAA-compliant telehealth. |
| Measure | Description | Time Frame |
|---|---|---|
| Association Between CY-BOCS-II Total Score and Orbitofrontal Cortex-Ventral Striatum Resting-State Functional Connectivity During Acute ERP | The primary outcome is the within-participant association between obsessive-compulsive disorder symptom severity and resting-state functional connectivity during the acute ERP phase. OCD symptom severity will be measured using the Children's Yale-Brown Obsessive Compulsive Scale, Second Edition total score. OFC-ventral striatum resting-state functional connectivity will be measured using Fisher z-transformed resting-state fMRI connectivity. The association will be estimated using visit-level linear mixed-effects models. CY-BOCS-II total scores range from 0 to 50, with higher scores indicating greater OCD symptom severity. | Baseline through end-of-acute ERP assessment visit, targeted Week 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in CY-BOCS-II Total Score at End of Acute ERP | Clinical symptom change will be measured as the change in Children's Yale-Brown Obsessive Compulsive Scale, Second Edition total score from baseline to the end-of-acute ERP assessment visit. CY-BOCS-II total scores range from 0 to 50, with higher scores indicating greater OCD symptom severity. A decrease in score indicates improvement. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jihoon Kim, MD, MSc | Contact | 862-414-3322 | gmj9009@med.cornell.edu |
| Name | Affiliation | Role |
|---|---|---|
| Conor Liston, MD, PhD | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NewYork-Presbyterian Hospital / Weill Cornell Medicine | New York | New York | 10065 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31734533 | Background | Jaspers-Fayer F, Lin SY, Chan E, Ellwyn R, Lim R, Best J, Belschner L, Lang D, Heran MKM, Woodward TS, Stewart SE. Neural correlates of symptom provocation in pediatric obsessive-compulsive disorder. Neuroimage Clin. 2019;24:102034. doi: 10.1016/j.nicl.2019.102034. Epub 2019 Oct 23. | |
| 9183141 | Background | Scahill L, Riddle MA, McSwiggin-Hardin M, Ort SI, King RA, Goodman WK, Cicchetti D, Leckman JF. Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997 Jun;36(6):844-52. doi: 10.1097/00004583-199706000-00023. |
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Individual participant data are not planned to be shared because this study enrolls minors and collects sensitive psychiatric, treatment-context, longitudinal clinical, and MRI/fMRI data. Given the small single-site sample and the potentially identifiable nature of repeated neuroimaging and clinical data, public sharing of participant-level data could create an unacceptable risk of re-identification or unintended disclosure. Aggregate results will be reported. Any future external data sharing would require separate IRB approval, consent/assent authorization or waiver as applicable, institutional data-use agreements, and appropriate de-identification or controlled-access safeguards.
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Single-arm, open-label behavioral intervention study in which all enrolled participants receive exposure and response prevention therapy and undergo repeated clinical and neuroimaging assessments. There is no randomization, comparator group, crossover, or factorial assignment.
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| Clinical Assessments | Other | Participants complete repeated clinical assessments according to the study schedule to evaluate obsessive-compulsive disorder symptom severity, symptom change, functioning, safety, and related clinical outcomes over time. Assessments may include clinician-administered ratings, participant-report measures, and other study outcome measures. These assessments are conducted for research and clinical monitoring purposes and are not intended as a therapeutic intervention. |
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| Research MRI Sessions | Diagnostic Test | Participants complete research magnetic resonance imaging sessions at scheduled study time points to acquire structural and functional MRI data, including functional MRI measures used to evaluate brain connectivity over time. Imaging sessions are used to examine changes in brain circuitry in relation to obsessive-compulsive disorder symptoms and treatment course. These sessions are conducted for research measurement purposes and are not intended to provide clinical diagnosis or treatment. |
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| Baseline to end-of-acute ERP assessment visit, targeted Week 14 |
| Number of Participants With Treatment-Emergent Adverse Events | Safety and tolerability will be assessed by the number and proportion of participants with treatment-emergent adverse events during study participation. Adverse events include unfavorable or unintended signs, symptoms, diseases, or worsening of pre-existing conditions temporally associated with study procedures, whether or not considered related to ERP, MRI/fMRI, symptom-reactivity tasks, or other study procedures. | From first study procedure through last study visit, up to 62 weeks |
| Change in CY-BOCS-II Total Score From End of Acute ERP to Last Booster or Maintenance Visit | Maintenance of clinical gains will be assessed as the change in Children's Yale-Brown Obsessive Compulsive Scale, Second Edition total score from the end-of-acute ERP assessment visit to the last booster or maintenance clinical assessment visit. CY-BOCS-II total scores range from 0 to 50, with higher scores indicating greater OCD symptom severity. A decrease in score indicates improvement, while an increase indicates symptom worsening. | End-of-acute ERP assessment visit, targeted Week 14, to last booster or maintenance clinical assessment visit, up to Week 62 |
| Change in OFC-Ventral Striatum Resting-State Functional Connectivity From End of Acute ERP to Last Booster or Maintenance Imaging Visit | Maintenance of neural change will be assessed as the change in orbitofrontal cortex-ventral striatum resting-state functional connectivity from the end-of-acute ERP imaging visit to the last booster or maintenance imaging visit. Resting-state functional connectivity will be derived from fMRI data and Fisher z-transformed for analysis. | End-of-acute ERP imaging visit, targeted Week 14, to last booster or maintenance imaging visit, up to Week 62 |
| 39232159 | Background | Lynch CJ, Elbau IG, Ng T, Ayaz A, Zhu S, Wolk D, Manfredi N, Johnson M, Chang M, Chou J, Summerville I, Ho C, Lueckel M, Bukhari H, Buchanan D, Victoria LW, Solomonov N, Goldwaser E, Moia S, Caballero-Gaudes C, Downar J, Vila-Rodriguez F, Daskalakis ZJ, Blumberger DM, Kay K, Aloysi A, Gordon EM, Bhati MT, Williams N, Power JD, Zebley B, Grosenick L, Gunning FM, Liston C. Frontostriatal salience network expansion in individuals in depression. Nature. 2024 Sep;633(8030):624-633. doi: 10.1038/s41586-024-07805-2. Epub 2024 Sep 4. |
| 28757305 | Background | Gordon EM, Laumann TO, Gilmore AW, Newbold DJ, Greene DJ, Berg JJ, Ortega M, Hoyt-Drazen C, Gratton C, Sun H, Hampton JM, Coalson RS, Nguyen AL, McDermott KB, Shimony JS, Snyder AZ, Schlaggar BL, Petersen SE, Nelson SM, Dosenbach NUF. Precision Functional Mapping of Individual Human Brains. Neuron. 2017 Aug 16;95(4):791-807.e7. doi: 10.1016/j.neuron.2017.07.011. Epub 2017 Jul 27. |
| 24840803 | Background | Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014 Jun;15(6):410-24. doi: 10.1038/nrn3746. |
| 26130211 | Background | McGuire JF, Piacentini J, Lewin AB, Brennan EA, Murphy TK, Storch EA. A META-ANALYSIS OF COGNITIVE BEHAVIOR THERAPY AND MEDICATION FOR CHILD OBSESSIVE-COMPULSIVE DISORDER: MODERATORS OF TREATMENT EFFICACY, RESPONSE, AND REMISSION. Depress Anxiety. 2015 Aug;32(8):580-93. doi: 10.1002/da.22389. Epub 2015 Jun 30. |
| 15507582 | Background | Pediatric OCD Treatment Study (POTS) Team. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA. 2004 Oct 27;292(16):1969-76. doi: 10.1001/jama.292.16.1969. |
| 22176943 | Background | Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jan;51(1):98-113. doi: 10.1016/j.jaac.2011.09.019. |
| ID | Term |
|---|---|
| D009771 | Obsessive-Compulsive Disorder |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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