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Overlapping Neural Circuits in Pediatric OCD

Primary Purpose

Obsessive Compulsive Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obsessive Compulsive Disorder focused on measuring OCD, Functional Magnetic Resonance Imaging (fMRI), Magnetic Resonance Imaging (MRI)

Eligibility Criteria

5 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

Patient Inclusion Criteria:

  • Participants must be 5-17 at the time of consent
  • Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnosis of OCD as the principal problem
  • Not on psychotropic medication and not receiving current psychotherapy for OCD
  • Written informed assent by the participants (8 and older) and consent by the parent
  • Participants and a parent/guardian must be able to read and understand English

Patient Exclusion Criteria:

  • DSM-IV current diagnosis of major depressive disorder, attention-deficit hyperactivity disorder, Tourette's/Tic Disorder, or substance/alcohol abuse
  • DSM-IV lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, or substance/alcohol abuse
  • Active suicidal ideation
  • Females who are pregnant or nursing
  • Major medical or neurological problems
  • Presence of metallic device or dental braces
  • IQ<80
  • A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
  • Individuals who are currently receiving CBT, other forms of psychotherapy, or psychotropic medications
  • Individuals who have received a full course of CBT in the past
  • A positive pregnancy test
  • Positive urine screen for illicit drugs
  • Inability of participant or parent/guardian to read or understand English

Healthy Control Inclusion Criteria:

  • Participants must be 5-17 at the time of consent
  • Written informed assent by the participants (8 and older) and consent by the parent
  • Participants and a parent/guardian must be able to read and understand English

Healthy Control Exclusion Criteria:

  • Any current or lifetime psychiatric diagnosis
  • Active suicidal ideation
  • Females who are pregnant or nursing
  • Major medical or neurological problems
  • Presence of metallic device or dental braces
  • IQ<80
  • A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
  • A positive pregnancy test
  • Positive urine screen for illicit drugs
  • Inability of participant or parent/guardian to read or understand English

Sites / Locations

  • NY State Psychiatric Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Participants With Obsessive-compulsive Disorder (OCD)

Healthy Control (HC) Participants

Arm Description

Children and adolescents who meet DSM-IV diagnostic criteria for OCD and had clinically significant obsessive-compulsive symptoms (CY-BOCS score>15). Comorbid anxiety disorders, but no other lifetime psychiatric diagnoses, were permitted in the OCD group as long as OCD was the primary diagnosis. Participants were unmedicated and had not received a full course of CBT with exposure and response prevention for OCD prior to their participation in the study. Following baseline assessment and scan, patients with OCD underwent a course of manualized treatment of CBT with E/RP adapted for pediatric OCD delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI.

Healthy control (HC) participants matched on age and sex with the OCD group. HC participants had no lifetime psychiatric disorders. HC participants were assessed and scanned at baseline and again after 12-16 weeks.

Outcomes

Primary Outcome Measures

Brain Activation Associated With the Resolution of Cognitive Conflict
Task-based functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) during their performance of a Simon Spatial Compatibility Task. In each trial, participants are presented with a leftward or rightward pointing arrow that is either congruent or incongruent with their position (left or right) on the screen. Participants are instructed to respond as quickly and accurately as possible to the direction in which the arrow was pointing by pressing a button on a response box using the index finger for left and the middle finger for right. Brain activation during the resolution of cognitive conflict is computed by contrasting blood-oxygen-level-dependent (BOLD) signal during Incongruent versus Congruent trials. BOLD signal is expressed in arbitrary units (A.U.s).

Secondary Outcome Measures

Functional Connectivity
Functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) at baseline and after approximately 16-20 weeks (i.e., post-treatment for the participants with OCD). The whole brain is divided in 352 brain regions comprised of 333 cortical surface (Gordon et al. Cereb Cortex 2016;26:288-303) and 19 subcortical (Fischl et al. Neuron 2002;53:341-55) parcellated regions. FC-strength (average of Fisher-r-to-Z transformed Pearson correlation coefficients) between each region was computed. Values >0 indicate regions are positively connected (synchronized), with larger values indicating stronger connection. Values <0 indicate regions are negatively connected (inversely synchronized), with more negative values stronger negative connection. A value of 0 indicates that the regions are not connected.
Brain Gray Matter Thickness
Structural MRI will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). Regional cortical thickness will be computed in the inferior frontal gyrus
Structural Connectivity (Streamline Counts)
Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). A structural connectivity matrix is estimated for each participant using the standard MRtrix3 preprocessing pipeline, yielding 164x164 symmetrical streamline count matrix for each participant using the FreeSurfer segmentations/parcellations noted above (148 cortical, 14 subcortical regions, and the left and right cerebellum). Using this approach, streamline count between brain regions is proportional to the cross-sectional area of white matter fibers connecting those regions. Thus, streamline count is a biologically plausible metric of "structural connectivity" proposed to represent the communication 'bandwidth' between regions.

Full Information

First Posted
April 9, 2015
Last Updated
August 9, 2023
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT02421315
Brief Title
Overlapping Neural Circuits in Pediatric OCD
Official Title
Overlapping Neural Circuits Implicated in Pediatric OCD
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
September 30, 2021 (Actual)
Study Completion Date
September 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to examine the brain functioning of children and adolescent with OCD before and after treatment with Exposure and Response Prevention (EXRP) therapy.
Detailed Description
The capacity to coordinate thoughts and actions to execute goal-directed behaviors (cognitive control) and the capacity to anticipate, respond to, and learn from reward (reward processing) are key processes for human behavior. Dysfunction in these processes has been hypothesized to contribute to repetitive thoughts and behaviors in many disorders, including obsessive-compulsive disorder (OCD), Tourette Syndrome (TS), and eating disorders. The investigators will use multimodal imaging to investigate neural circuits that support cognitive control and reward processing, using pediatric OCD as a model system. The short-term goal is to clarify how circuit-based abnormalities contribute to repetitive thoughts/behaviors; these data will inform future trans-diagnostic studies. The long-term goal is to identify control and reward circuit-abnormalities as targets for new trans-diagnostic treatments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive Compulsive Disorder
Keywords
OCD, Functional Magnetic Resonance Imaging (fMRI), Magnetic Resonance Imaging (MRI)

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Participants With Obsessive-compulsive Disorder (OCD)
Arm Type
Experimental
Arm Description
Children and adolescents who meet DSM-IV diagnostic criteria for OCD and had clinically significant obsessive-compulsive symptoms (CY-BOCS score>15). Comorbid anxiety disorders, but no other lifetime psychiatric diagnoses, were permitted in the OCD group as long as OCD was the primary diagnosis. Participants were unmedicated and had not received a full course of CBT with exposure and response prevention for OCD prior to their participation in the study. Following baseline assessment and scan, patients with OCD underwent a course of manualized treatment of CBT with E/RP adapted for pediatric OCD delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI.
Arm Title
Healthy Control (HC) Participants
Arm Type
No Intervention
Arm Description
Healthy control (HC) participants matched on age and sex with the OCD group. HC participants had no lifetime psychiatric disorders. HC participants were assessed and scanned at baseline and again after 12-16 weeks.
Intervention Type
Behavioral
Intervention Name(s)
CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment
Intervention Description
CBT treatment consisted of 12-16 hour-long sessions. For exceptional cases not showing clinical improvement after six CBT treatment sessions, complementary pharmacological treatment (SSRI) was offered as part of our treatment protocol. CBT for OCD involves gradually exposing patients to anxiety provoking stimuli while having patients refrain from engaging in compulsive rituals and/or avoidance behaviors. There are three major components of CBT treatment for OCD, specifically: (1) exposure to anxiety provoking stimuli, (2) response prevention, and (3) cognitive techniques intended to decrease anxiety during the exposure and response prevention processes.
Primary Outcome Measure Information:
Title
Brain Activation Associated With the Resolution of Cognitive Conflict
Description
Task-based functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) during their performance of a Simon Spatial Compatibility Task. In each trial, participants are presented with a leftward or rightward pointing arrow that is either congruent or incongruent with their position (left or right) on the screen. Participants are instructed to respond as quickly and accurately as possible to the direction in which the arrow was pointing by pressing a button on a response box using the index finger for left and the middle finger for right. Brain activation during the resolution of cognitive conflict is computed by contrasting blood-oxygen-level-dependent (BOLD) signal during Incongruent versus Congruent trials. BOLD signal is expressed in arbitrary units (A.U.s).
Time Frame
single time point: baseline
Secondary Outcome Measure Information:
Title
Functional Connectivity
Description
Functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) at baseline and after approximately 16-20 weeks (i.e., post-treatment for the participants with OCD). The whole brain is divided in 352 brain regions comprised of 333 cortical surface (Gordon et al. Cereb Cortex 2016;26:288-303) and 19 subcortical (Fischl et al. Neuron 2002;53:341-55) parcellated regions. FC-strength (average of Fisher-r-to-Z transformed Pearson correlation coefficients) between each region was computed. Values >0 indicate regions are positively connected (synchronized), with larger values indicating stronger connection. Values <0 indicate regions are negatively connected (inversely synchronized), with more negative values stronger negative connection. A value of 0 indicates that the regions are not connected.
Time Frame
single time point: Baseline
Title
Brain Gray Matter Thickness
Description
Structural MRI will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). Regional cortical thickness will be computed in the inferior frontal gyrus
Time Frame
Single time point: Baseline
Title
Structural Connectivity (Streamline Counts)
Description
Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). A structural connectivity matrix is estimated for each participant using the standard MRtrix3 preprocessing pipeline, yielding 164x164 symmetrical streamline count matrix for each participant using the FreeSurfer segmentations/parcellations noted above (148 cortical, 14 subcortical regions, and the left and right cerebellum). Using this approach, streamline count between brain regions is proportional to the cross-sectional area of white matter fibers connecting those regions. Thus, streamline count is a biologically plausible metric of "structural connectivity" proposed to represent the communication 'bandwidth' between regions.
Time Frame
Single time point (baseline)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Patient Inclusion Criteria: Participants must be 5-17 at the time of consent Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnosis of OCD as the principal problem Not on psychotropic medication and not receiving current psychotherapy for OCD Written informed assent by the participants (8 and older) and consent by the parent Participants and a parent/guardian must be able to read and understand English Patient Exclusion Criteria: DSM-IV current diagnosis of major depressive disorder, attention-deficit hyperactivity disorder, Tourette's/Tic Disorder, or substance/alcohol abuse DSM-IV lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, or substance/alcohol abuse Active suicidal ideation Females who are pregnant or nursing Major medical or neurological problems Presence of metallic device or dental braces IQ<80 A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) Individuals who are currently receiving CBT, other forms of psychotherapy, or psychotropic medications Individuals who have received a full course of CBT in the past A positive pregnancy test Positive urine screen for illicit drugs Inability of participant or parent/guardian to read or understand English Healthy Control Inclusion Criteria: Participants must be 5-17 at the time of consent Written informed assent by the participants (8 and older) and consent by the parent Participants and a parent/guardian must be able to read and understand English Healthy Control Exclusion Criteria: Any current or lifetime psychiatric diagnosis Active suicidal ideation Females who are pregnant or nursing Major medical or neurological problems Presence of metallic device or dental braces IQ<80 A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) A positive pregnancy test Positive urine screen for illicit drugs Inability of participant or parent/guardian to read or understand English
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachel Marsh, Ph.D.
Organizational Affiliation
New York Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
NY State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
35485920
Citation
Wang Z, Fontaine M, Cyr M, Rynn MA, Simpson HB, Marsh R, Pagliaccio D. Subcortical shape in pediatric and adult obsessive-compulsive disorder. Depress Anxiety. 2022 Jun;39(6):504-514. doi: 10.1002/da.23261. Epub 2022 Apr 29.
Results Reference
derived
PubMed Identifier
34539777
Citation
Lv D, Ou Y, Wang Y, Ma J, Zhan C, Yang R, Chen Y, Shang T, Jia C, Sun L, Zhang G, Sun Z, Li J, Wang X, Guo W, Li P. Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder. Neural Plast. 2021 Sep 8;2021:3741104. doi: 10.1155/2021/3741104. eCollection 2021.
Results Reference
derived
PubMed Identifier
31952071
Citation
Cyr M, Pagliaccio D, Yanes-Lukin P, Fontaine M, Rynn MA, Marsh R. Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Neuropsychopharmacology. 2020 Jun;45(7):1232-1240. doi: 10.1038/s41386-020-0613-3. Epub 2020 Jan 17. Erratum In: Neuropsychopharmacology. 2020 Mar 4;:
Results Reference
derived
PubMed Identifier
31889307
Citation
Pagliaccio D, Cha J, He X, Cyr M, Yanes-Lukin P, Goldberg P, Fontaine M, Rynn MA, Marsh R. Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder. J Child Psychol Psychiatry. 2020 Dec;61(12):1299-1308. doi: 10.1111/jcpp.13191. Epub 2019 Dec 31.
Results Reference
derived

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Overlapping Neural Circuits in Pediatric OCD

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