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| ID | Type | Description | Link |
|---|---|---|---|
| 5R21MH101395-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children with OCD | Experimental | Children with obsessive compulsive disorder, not currently on medication for OCD |
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| Healthy Control Children | Active Comparator | Children without obsessive compulsive disorder |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sertraline | Drug | Impact of sertraline on functional brain connectivity |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
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Inclusion Criteria (OCD):
Exclusion Criteria (OCD):
Inclusion Criteria (Controls):
Exclusion criteria (controls):
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| Name | Affiliation | Role |
|---|---|---|
| Gail A Bernstein, MD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55454 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26674413 | Result | 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 Res Neuroimaging. 2016 Jan 30;247:49-56. doi: 10.1016/j.pscychresns.2015.11.002. Epub 2015 Nov 19. | |
| 30768407 | Derived | Bernstein GA, Cullen KR, Harris EC, Conelea CA, Zagoloff AD, Carstedt PA, Lee SS, Mueller BA. Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With Obsessive-Compulsive Disorder: A Pilot Study. J Am Acad Child Adolesc Psychiatry. 2019 May;58(5):486-495. doi: 10.1016/j.jaac.2018.07.897. Epub 2018 Oct 30. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Obsessive-compulsive Disorder | Sertraline: Impact of sertraline on functional brain connectivity |
| FG001 | Healthy Controls | No Intervention: Healthy control non-intervention |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Obsessive-compulsive Disorder | Sertraline: Impact of sertraline on functional brain connectivity |
| BG001 | Healthy Controls | No Intervention: Healthy control non-intervention |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 2 additional participants with OCD and 1 Healthy Control were removed from this analysis due to motion effects in the neuroimaging data. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Obsessive-compulsive Disorder | Sertraline: Impact of sertraline on functional brain connectivity |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Medication Side Effect | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Gail Bernstein | University of Minnesota | 612-625-1632 | berns001@umn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 10, 2017 | Apr 24, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020280 | Sertraline |
| ID | Term |
|---|---|
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
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| No Intervention | Other | Healthy control non-intervention |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| CY-BOCS Total Score at Baseline | 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. | Mean | Standard Deviation | units on a scale |
|
| OG000 |
| Children With OCD |
Sertraline: Impact of sertraline on functional brain connectivity |
| OG001 | Healthy Control Children | No Intervention: Healthy control non-intervention |
|
|
| 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. | 2 additional participants with OCD and 1 Healthy Control were removed from this analysis due to motion effects in the neuroimaging data. | Posted | Mean | Standard Deviation | z score | 12 weeks |
|
|
|
|
| 0 |
| 23 |
| 1 |
| 23 |
| 8 |
| 23 |
| EG001 | Healthy Controls | No Intervention: Healthy control non-intervention | 0 | 18 | 0 | 18 | 0 | 18 |
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| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| Connectivity z-scores for left putamen at baseline |
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| Connectivity z-scores for left putamen at week 12 |
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