Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD

NCT04131829 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 20000236881R01MH116038-01A11K24MH121571-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder

Outcome Measures

Primary Outcomes (1)

• Obsessive-compulsive severity change

  Yale-Brown Obsessive-Compulsive Scale (Y-BOCS);72,73 -This is a checklist and Clinician administered - 10 item severity scale, from none to extreme. Total severity score range is 0 to 40. This will be presented as % improvement in Y-BOCS as a continuous measure of treatment response, rather than an artificially dichotomized measure of 'response', in all analyses. This the primary outcome measure of change across the study treatment and scans.

  18 weeks

Secondary Outcomes (7)

• Tic severity change

  18 weeks

• Beck Depression Inventory-II

  18 weeks

• Anxiety

  18 weeks

• Obsessive-compulsive concerns

  18 weeks

• Magical ideation

  18 weeks

Study Arms (2)

Healthy Controls

NO INTERVENTION

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.

OCD Group

EXPERIMENTAL

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.

Drug: Fluoxetine - immediate treatment; Drug: Fluoxetine - delayed treatment

Interventions

Fluoxetine - immediate treatment 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.

Also known as: fluoxetine, prozac

OCD Group

Fluoxetine - delayed treatment 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.

Also known as: fluoxetine, prozac

OCD Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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.

Sponsors & Collaborators

• Yale University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

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

New Haven, Connecticut, 06519, United States

RECRUITING

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Christopher Pittenger, MD, PhD

  Professor of Psychiatry; Director, Yale OCD Research Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yale OCD Research Clinic

CONTACT

1-855-623-9253; ocd.research@yale.edu

Stephen Kichuk, MPH

CONTACT

203-974-7534; stephen.kichuk@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 18, 2019
• Study Start: October 14, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)