Trial Outcomes & Findings for Overlapping Neural Circuits in Pediatric OCD (NCT NCT02421315)

Last Updated: 2023-08-30

Results Overview

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).

Recruitment status

COMPLETED

Study phase

Target enrollment

55 participants

Primary outcome timeframe

single time point: baseline

Results posted on

2023-08-30

Participant Flow

Participant milestones

Participant milestones
Measure	Participants With Obsessive-compulsive Disorder (OCD) 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants 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 .
Overall Study STARTED	28	27
Overall Study COMPLETED	23	15
Overall Study NOT COMPLETED	5	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Overlapping Neural Circuits in Pediatric OCD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With Obsessive-compulsive Disorder (OCD) n=28 Participants 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants n=27 Participants 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.	Total n=55 Participants Total of all reporting groups
Age, Continuous	12.14 years STANDARD_DEVIATION 3.34 • n=5 Participants	11.26 years STANDARD_DEVIATION 3.23 • n=7 Participants	11.69 years STANDARD_DEVIATION 3.23 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	16 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	8 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	27 participants n=7 Participants	55 participants n=5 Participants
Full Scale Intelligence Quotient (FSIQ)	106.96 T-Score STANDARD_DEVIATION 16.20 • n=5 Participants	109.59 T-Score STANDARD_DEVIATION 12.14 • n=7 Participants	108.25 T-Score STANDARD_DEVIATION 13.95 • n=5 Participants

PRIMARY outcome

Timeframe: single time point: baseline

Population: Only participants with usable fMRI data were included in these analyses. One participant with OCD and 4 HC participants were excluded because of missing fMRI data.

Outcome measures

Outcome measures
Measure	Participants With Obsessive-compulsive Disorder (OCD) n=27 Participants 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants n=23 Participants 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.
Brain Activation Associated With the Resolution of Cognitive Conflict	.7 Arbitrary units Standard Deviation .2	.59 Arbitrary units Standard Deviation .2

SECONDARY outcome

Timeframe: single time point: Baseline

Population: Only participants with usable fMRI data were included in these analyses. Three participants with OCD and 4 HC participants were excluded because of missing fMRI data.

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.

Outcome measures

Outcome measures
Measure	Participants With Obsessive-compulsive Disorder (OCD) n=25 Participants 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants n=23 Participants 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.
Functional Connectivity	-0.312768356 arbitrary units Standard Deviation 0.223710827	0.182360856 arbitrary units Standard Deviation 0.230155947

SECONDARY outcome

Timeframe: Single time point: Baseline

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

Outcome measures

Outcome measures
Measure	Participants With Obsessive-compulsive Disorder (OCD) n=28 Participants 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants n=27 Participants 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.
Brain Gray Matter Thickness	3 mm Standard Deviation 0.2	2.89 mm Standard Deviation 0.2

SECONDARY outcome

Timeframe: Single time point (baseline)

Population: Only participants with usable DTI data were included in these analyses. Three participants with OCD and 2 HC participants were excluded because of missing DTI data.

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.

Outcome measures

Outcome measures
Measure	Participants With Obsessive-compulsive Disorder (OCD) n=26896 streamlines 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 (March \& Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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.	Healthy Control (HC) Participants n=26896 streamlines 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.
Structural Connectivity (Streamline Counts)	227.688 streamlines Standard Deviation 86.169	328.224 streamlines Standard Deviation 112.684

Adverse Events

Participants With Obsessive-compulsive Disorder (OCD)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Control (HC) Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Rachel Marsh

New York State Psychiatric Institute

Phone: 646-774-5774

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place