OCDPhase 1/2NCT02797808
Effects of Sertraline on Brain Connectivity in Adolescents With OCD
A Phase 1/2 study testing Sertraline in people with OCD, run by University of Minnesota at 1 site in United States.
Trial summary
The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample. Read more about this study
- Who is it for?
- Ages 8 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- OCD
- What is being tested?
- Sertraline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to 31 Jan 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
- Healthy 8-17 year olds
Who cannot join
- 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
Show all 10Show fewer
- positive pregnancy test
- history of seizure disorder or serious head injury
- No psychiatric diagnoses
- No immediate family history of OCD
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55454
About this study
Official title: Effects of Sertraline on Brain Connectivity in Adolescents With OCD (Obsessive-Compulsive Disorder)
The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample.
Read the 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).
- Conditions
- OCD
- Being tested
- Sertraline, No Intervention
- Keywords
- OCD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
Also called Zoloft
Impact of sertraline on functional brain connectivity
No InterventionOther
Healthy control non-intervention
| Study group | Role | What they receive |
|---|---|---|
| Children with OCD | Experimental | Children with obsessive compulsive disorder, not currently on medication for OCD Receives: Drug: Sertraline |
| Healthy Control Children | Active comparator | Children without obsessive compulsive disorder Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study startAug 2013
- Primary completion31 Jan 2017
- Study completion31 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OCDStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Gail A Bernstein, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797808
- Sponsor's protocol ID
- 1105M99532
- Other IDs
- 5R21MH101395-02
- Status last verified
- Dec 2020
- First submitted
- 8 Jun 2016
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 26674413Bernstein 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.
PubMed 30768407
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sertraline on Brain Connectivity in Adolescents With OCD (Obsessive-Compulsive Disorder)
- ClinicalTrials.gov ID
- NCT02797808
- Acronym / sponsor ID
- 1105M99532
- Conditions
- OCD
- Keywords
- OCD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2013
- Primary completion
- 31 Jan 2017 (actual)
- Study completion
- 31 Jan 2017 (actual)
- First posted
- 13 Jun 2016 (estimated)
- Results
- Posted 5 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Children with OCD | Experimental | Drug: SertralineChildren with obsessive compulsive disorder, not currently on medication for OCD |
| Healthy Control Children | Active comparator | Other: No InterventionChildren without obsessive compulsive disorder |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
- Healthy 8-17 year olds
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SertralineAlso: ZoloftImpact of sertraline on functional brain connectivity | Drug | Children with OCD |
| No InterventionHealthy control non-intervention | Other | Healthy Control Children |
Primary outcome
CY-BOCS Total Score at 12-weeks
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26674413Bernstein 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.
- Derived from this study: PubMed 30768407Bernstein 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail A Bernstein, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sertraline in people with OCD, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CY-BOCS Total Score at 12-weeks (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02797808, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.