Overlapping Neural Circuits in Pediatric OCD

Obsessive Compulsive Disorder Clinical Trial

Official title:

Overlapping Neural Circuits Implicated in Pediatric OCD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02421315
• Other study ID #: 7006
• Secondary ID: R21MH101441
• Status: Completed
• Phase: N/A
• Start date: October 2014
• Est. completion date: September 30, 2021

Study information

• Verified date: August 2023
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Obsessive Compulsive Disorder
• Obsessive-Compulsive Disorder

Intervention

Behavioral:
• CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment
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.

Locations

Country	Name	City	State
United States	NY State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	single time point: baseline
Secondary	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.	single time point: Baseline
Secondary	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	Single time point: Baseline
Secondary	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.	Single time point (baseline)