Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD

NCT ID: NCT04131829

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2026-12-31

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.

Conditions

Obsessive-Compulsive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Healthy Controls

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

OCD Group

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.

Group Type: EXPERIMENTAL

Fluoxetine - immediate treatment

Intervention Type: DRUG

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.

Fluoxetine - delayed treatment

Intervention Type: DRUG

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.

Interventions

Fluoxetine - immediate treatment

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.

Intervention Type: DRUG

Fluoxetine - delayed treatment

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.

Intervention Type: DRUG

Other Intervention Names

fluoxetine, prozac; fluoxetine, prozac

Eligibility Criteria

Inclusion Criteria

(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.

• 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

(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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Pittenger, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Psychiatry; Director, Yale OCD Research Clinic

Locations

Yale OCD Research Clinic - CMHC/CNRU, 34 Park ST

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yale OCD Research Clinic

Role: CONTACT

ocd.research@yale.edu

1-855-623-9253

Stephen Kichuk, MPH

Role: CONTACT

stephen.kichuk@yale.edu

203-974-7534

Facility Contacts

Stephen Kichuk, MPH

Role: primary

stephen.kichuk@yale.edu

203-974-7534

OCD Research

Role: backup

ocd.research@yale.edu

1-855-623-9253

Other Identifiers

1R01MH116038-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1K24MH121571-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000023688

Identifier Type: -

Identifier Source: org_study_id