OCD
Conditions
Keywords
OCD
Brief summary
The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample.
Detailed 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).
Interventions
DRUGSertraline
Impact of sertraline on functional brain connectivity
OTHERNo Intervention
Healthy control non-intervention
Sponsors
National Institute of Mental Health (NIMH)
University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CY-BOCS Total Score at 12-weeks | 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. |
| Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obsessive-compulsive Disorder Sertraline: Impact of sertraline on functional brain connectivity | 23 |
| Healthy Controls No Intervention: Healthy control non-intervention | 18 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 6 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Obsessive-compulsive Disorder | Healthy Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 23 Participants | 18 Participants | 41 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.4 years STANDARD_DEVIATION 2.6 | 13.4 years STANDARD_DEVIATION 2.9 | 13.4 years STANDARD_DEVIATION 2.75 |
| CY-BOCS Total Score at Baseline | 24.8 units on a scale STANDARD_DEVIATION 6.9 | 0 units on a scale STANDARD_DEVIATION 0 | 24.8 units on a scale STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 18 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) White | 10 Participants | 13 Participants | 23 Participants |
| Region of Enrollment United States | 23 Participants | 18 Participants | 41 Participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 18 |
| other Total, other adverse events | 8 / 23 | 0 / 18 |
| serious Total, serious adverse events | 1 / 23 | 0 / 18 |
Outcome results
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.
Time frame: 12 weeks
Population: 2 additional participants with OCD and 1 Healthy Control were removed from this analysis due to motion effects in the neuroimaging data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Children With OCD | CY-BOCS Total Score at 12-weeks | 14.1 units on a scale | Standard Deviation 8.5 |
| Healthy Control Children | CY-BOCS Total Score at 12-weeks | 0 units on a scale | Standard Deviation 0 |
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.
Time frame: 12 weeks
Population: 2 additional participants with OCD and 1 Healthy Control were removed from this analysis due to motion effects in the neuroimaging data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Children With OCD | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for right putamen at baseline | 0.15 z score | Standard Deviation 1.04 |
| Children With OCD | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for right putamen at 12 weeks | 1.89 z score | Standard Deviation 0.85 |
| Children With OCD | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for left putamen at baseline | 1.46 z score | Standard Deviation 1.14 |
| Children With OCD | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for left putamen at week 12 | 3.03 z score | Standard Deviation 1.54 |
| Healthy Control Children | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for left putamen at week 12 | 0.89 z score | Standard Deviation 0.99 |
| Healthy Control Children | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for right putamen at baseline | 1.44 z score | Standard Deviation 1.06 |
| Healthy Control Children | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for left putamen at baseline | 2.41 z score | Standard Deviation 1.19 |
| Healthy Control Children | Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Connectivity z-scores for right putamen at 12 weeks | 0.60 z score | Standard Deviation 0.98 |
p-value: <0.0083ANOVA