Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD

Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD

Sponsors

Lead sponsor: Yale University

Collaborator: National Institute of Mental Health (NIMH)

Source Yale University
Brief Summary

The proposed randomized, double-blind research study will use functional magnetic resonance neuroimaging using state-of-the-art HCP acquisition protocols and analytic pipelines, to identify predictors and correlates of response to an accepted first-line pharmacological treatment for obsessive-compulsive disorder.

Detailed Description

The proposed study intends to recruit 2 groups:

1. Matched healthy control participants will be imaged with one fMRI at baseline as a no-treatment comparison group; and

2. a randomized, double-blind group of unmedicated OCD participants who will be assigned to begin either immediate or placebo-delayed treatment, and who will be imaged with fMRIs at baseline and over the course of treatment with a selective serotonin reuptake inhibitor (SSRI), fluoxetine.

Hypothesis-driven analyses and exploratory analyses will be performed in parallel.

This study will address the following Specific Aims:

1. Identification of neural dysconnectivity associated with OCD symptomatology.

2. Characterizing neural markers of clinical response to SSRI pharmacotherapy.

3. Mapping neural predictors of clinical response to pharmacotherapy.

Overall Status Recruiting
Start Date October 15, 2019
Completion Date April 30, 2026
Primary Completion Date October 31, 2025
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Obsessive-compulsive severity change 12 weeks
Secondary Outcome
Measure Time Frame
Tic severity change 12 weeks
Obsessive-compulsive Inventory 12 weeks
Anxiety 12 weeks
Obsessive-compulsive concerns 12 weeks
Beliefs Conviction and Insight 12 weeks
Magical ideation 12 weeks
Sensory phenomena 12 weeks
"Not Just Right" experiences and sensations in OCD 12 weeks
Enrollment 120
Condition
Intervention

Intervention type: Drug

Intervention name: Fluoxetine - immediate treatment

Description: Following the Baseline assessment, OCD subjects will be randomized to receive either immediate fluoxetine monotherapy or delayed fluoxetine, after a 6-week placebo lead-in.

Arm group label: OCD Group

Other name: fluoxetine, prozac

Intervention type: Drug

Intervention name: Fluoxetine - delayed treatment

Description: Following the Baseline assessment, OCD subjects will be randomized to receive either immediate fluoxetine monotherapy or delayed fluoxetine, after a 6-week placebo lead-in.

Arm group label: OCD Group

Other name: fluoxetine, prozac

Eligibility

Criteria:

Inclusion Criteria:

- Inclusion criteria for all groups will include: (i) Adults, Men and women will be included, in a 1:1 ratio; and efforts will be made to recruit racial and ethnic subgroups. Groups will be further matched on age, handedness; and later, in analysis, on educational status and smoking history.

(ii) signed informed consent, approved by the Yale Human Investigations Committee; and (iii) ability and willingness to participate in all study procedures, including clinical assessments and fMRI scans.

- Additional inclusion criteria:

- OCD Participants:

(i) a DSM diagnosis of OCD, established as detailed above; (ii) a baseline Y-BOCS of ≥16; (iii) no current psychoactive medication, with the exception of the occasional use of a PRN medication for sleep; (iv) treatment seeking, and clinically appropriate for fluoxetine pharmacotherapy; (v) for women of childbearing potential, not pregnant or intending to become pregnant, and willing to use reliable birth control over the course of the study, either prescribed contraceptive (oral contraceptive, injectable, or implant) or one barrier method (e.g. diaphragm with spermicide, intrauterine device, cervical cap). Women of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy tests at the study baseline and on each scan day appointment prior to the MRI scan.

- Healthy Control Participants:

(i) no current DSM diagnosis (by clinician interview confirmed by SCID or MINI); (ii) no documented or clinically suspected family history in a first- or second- degree relative of OCD, Tourette syndrome, hoarding disorder, body dysmorphic disorder, or a compulsive grooming disorder.

Exclusion Criteria:

- Exclusion criteria for all groups will include:

(i) any unstable medical, psychiatric, or neurological condition (including active or otherwise problematic suicidality) that may necessitate urgent treatment; (ii) any substance use disorder within the past 6 months; (iii) use of psychotropic medications within the past 8 weeks, with the exception of occasional use of a sleep aid or analgesic; (iv) use of an as-needed sleep aid or prescription analgesic within 3 days of the scan; (v) any history of a primary psychotic disorder or of mania; (vi) any evidence of substance use on urine toxicology testing; (vii) any major neurological disease or history of major head trauma, including concussion with extended loss of consciousness; (viii) pregnancy; (ix) any metal in the body or other contraindication to MRI scanning; (x) severe claustrophobia, back pain, or other condition that may make an extended MR scan difficult or lead to excessive movement during the scan.

- Additional exclusion criteria:

- OCD Participants:

(i) past allergy or adverse reaction to fluoxetine or another SSRI, or other clinical contraindication to fluoxetine pharmacotherapy; (ii) documented nonresponse to a past trial of fluoxetine of appropriate dose (≥40 mg/dy) and duration (≥12 weeks).

(iii) Patients taking Coumadin or Monoamine oxidase inhibitors (MAOIs) will be excluded from the study.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Christopher Pittenger, MD, PhD Principal Investigator Associate Professor of Psychiatry; Director, Yale OCD Research Clinic
Overall Contact

Last name: Yale OCD Research Clinic

Phone: 1-855-623-9253

Email: [email protected]

Location
facility status contact contact_backup Yale OCD Research Clinic - CMHC/CNRU, 34 Park ST Richard Baker, BA 855-623-9253 [email protected]
Location Countries

United States

Verification Date

October 2019

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Healthy Controls

Arm group type: No Intervention

Description: The healthy control group will be an age matched sample of unmedicated healthy adults who will be recruited and imaged once at baseline and the data compared with that of OCD subjects at baseline.

Arm group label: OCD Group

Arm group type: Experimental

Description: The OCD group will comprise of unmedicated individuals with clinically significant OCD symptoms. OCD Subjects will be randomized, double-blind, to receive immediate or delayed (by 6 weeks as a placebo lead-in) pharmacotherapy.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: 80 OCD patients and 40 healthy participants matched on demographics will be recruited and asked to complete Structural (sMRI) and Functional (fMRI) Magnetic Resonance Imaging. Patients with OCD will be randomized to immediate monotherapy or 6-week placebo-delayed monotherapy, with fluoxetine.

Primary purpose: Basic Science

Masking: Double (Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov