Effects of Sertraline on Brain Connectivity in Adolescents With OCD

OCD Clinical Trial

Official title:

Effects of Sertraline on Brain Connectivity in Adolescents With OCD (Obsessive-Compulsive Disorder)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02797808
• Other study ID #: 1105M99532
• Secondary ID: 5R21MH101395-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2013
• Est. completion date: January 31, 2017

Study information

• Verified date: December 2020
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample.

Description:

To examine FSTC using advanced multi-modal imaging techniques, including resting-state functional magnetic resonance imaging (R-fMRI) and high angular resolution diffusion imaging (HARDI), in 25 medication-free adolescents youths with OCD (ages 8-17) in comparison with 25 matched healthy controls.

Hypotheses: (A) Based on the pilot data, adolescents youths with OCD will show lower functional connectivity in FSTC at baseline when compared with controls, and , lower functional connectivity in FSTC will correlate with greater severity on CY-BOCS. (B) Adolescents Youths with OCD will also show abnormalities in structural connectivity in FSTC at baseline when compared with controls, and structural and functional connectivity will be related. (C) The investigators will explore relations between OCD dimensions and functional connectivity measures, and predict that the repeating/ordering dimension will correlate with orbitofrontal cortex (OFC) connections, hoarding will correlate with rostral anterior cingulate cortex (ACC) connections, and forbidden thoughts will correlate with caudal ACC connections.

To investigate how sertraline impacts functional connectivity in FSTC in adolescents with OCD.

Hypothesis: After 12 weeks of sertraline treatment, functional connectivity measures within FSTC for the OCD group will (on average) increase compared to baseline and will no longer be significantly different when compared with controls. Non-responders may show a different pattern (i.e. failure to show these changes).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 31, 2017
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

Inclusion Criteria (OCD):

• OCD as the primary Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis based on the Anxiety Disorders Interview Schedule (ADIS) for DSM-IV, Child Version

• Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score of greater than 15

Exclusion Criteria (OCD):

• lifetime diagnosis of bipolar disorder, schizophrenia, or substance abuse/dependence on ADIS

• Intelligence Quotient (IQ) < 80 on Wechsler Abbreviated Scales of Intelligence (WASI)

• positive urine drug screen

• MRI-incompatible features (e.g., metal implants, claustrophobia)

• current or recent trial of psychotropic medication (within the past 4 8 weeks or past 6 12 weeks for fluoxetine)

• non-response in > 2 selective serotonin reuptake inhibitor (SSRI) trials of adequate dose/duration

• positive pregnancy test

• history of seizure disorder or serious head injury

Inclusion Criteria (Controls):

• Healthy 8-17 year olds

Exclusion criteria (controls):

• No psychiatric diagnoses

• No immediate family history of OCD

Related Conditions & MeSH terms

• OCD

Intervention

Drug:
• Sertraline
Impact of sertraline on functional brain connectivity

Other:
• No Intervention
Healthy control non-intervention

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Bernstein GA, Mueller BA, Schreiner MW, Campbell SM, Regan EK, Nelson PM, Houri AK, Lee SS, Zagoloff AD, Lim KO, Yacoub ES, Cullen KR. Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder. Psychiatry Re — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CY-BOCS Total Score at 12-weeks	The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) a clinician-rated semi-structured instrument assessing OCD severity over the previous 7 days in children ages 6 to 17 years. Items are scored from 0 (none) to 4 (extreme) and total score ranges from 0 to 40 with higher scores indicating greater impairment. All 19 items are rated, but only items 1-10 are used to determine the total score. The total CY-BOCS score is the sum of items 1-10; the obsession and compulsion subtotals are the sums of items 1-5 and 6-10, respectively. At this time, items 1A and 6A are not being used in the scoring. Items 17 (global severity) and 18 (global improvement) are adapted from the Clinical Global Impression Scale to provide measures of overall functional impairment associated with the presence of obsessive-compulsive symptoms.	12 weeks
Primary	Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses	Participants had whole brain fMRI at baseline &12 weeks. Whole brain connectivity in 6 striatal ROIs was performed. Two-way mixed effects ANOVAs were performed with FEAT. Clusters were significant if p <.0042 based on .05/(6 ROIs x 2 tests/ROI). Mean z-score was found for each time point in each subject's connectivity map in each significant cluster. Within-group paired-sample t tests examined RSFC change over time in these metrics for each group. To investigate group X time interactions from the 2-way ANOVA, we compared mean z-scores within each significant cluster at baseline & 12 weeks. Resulting numbers represented striatal connectivity for each individual at each time point. Within group paired sample t-tests examined RSFC change over time for each group. Bonferroni correction was applied to alpha level (2-tailed, p<0.5/6 =.0083) for multiple testing. We do not have an a priori hypothesis as to whether increase or decrease in RSFC is a better outcome. Unit of measure is z-score.	12 weeks