Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD

• ClinicalTrials.gov Identifier: NCT04131829
• Recruitment Status: Recruiting
• First Posted: October 18, 2019
• Last Update Posted: December 7, 2022
• Sponsor: Yale University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Yale University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obsessive-Compulsive Disorder	Drug: Fluoxetine - immediate treatment; Drug: Fluoxetine - delayed treatment	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• 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.
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD
• Actual Study Start Date: October 14, 2019
• Estimated Primary Completion Date: June 1, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
No Intervention: 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.
Experimental: 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.	Drug: 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.; Other Name: fluoxetine, prozac; 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.; Other Name: fluoxetine, prozac

Outcome Measures

Primary Outcome Measures :

1. Obsessive-compulsive severity change [ Time Frame: 12 weeks ]
   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.

Secondary Outcome Measures :

1. Tic severity change [ Time Frame: 12 weeks ]
   Yale Global Tic Severity Scale (YGTSS) will be used to measure Tic severity. It is a clinician administered instrument with a score from 0 to 25- 25 being the most severe.
2. Obsessive-compulsive Inventory [ Time Frame: 12 weeks ]
   Obsessive Compulsive Inventory-Revised (OCI-R);81 18 items scored 0 to 4, combined into 6 subscales (of 3 items each) and a total score (up to 72).
3. Anxiety [ Time Frame: 12 weeks ]
   Beck Anxiety Inventory (BAI);83 21 item self report on a 4 point Likert scale - 0 (not at all) to 3 (severely).
4. Obsessive-compulsive concerns [ Time Frame: 12 weeks ]
   Dimensional Obsessive-Compulsive Scale (DOCS);84 20 questions, asks about 4 categories of obsessive-compulsive concerns (each consists of 5 items scored on a Likert scale of 0-no symptoms to 4 - extreme symptoms) over the previous month.
5. Beliefs Conviction and Insight [ Time Frame: 12 weeks ]
   Brown Assessment of Beliefs Scale (BABS);85 clinician rated, semi-structured measure of degree of conviction and insight concerning beliefs in 7 areas, covering the past week, and scored from 0 to 4 (least to most severe), with the total score based on first 6 items with a range of 0 to 24.
6. Magical ideation [ Time Frame: 12 weeks ]
   Magical Ideation Scale (MIS);86 30 item true / false scale, assessing erroneous beliefs based on magical thinking.
7. Sensory phenomena [ Time Frame: 12 weeks ]
   University of São Paulo Sensory Phenomena Scale (USP-SPS)
8. "Not Just Right" experiences and sensations in OCD [ Time Frame: 12 weeks ]
   Not Just Right Experiences Questionnaire Revised (INC).88 19 Questions: Rate 10 NJR Experiences; Choose most recent one; Identify how long ago it occurred; then complete 7 dimensional ratings of that NJRE: frequency, intensity, immediate distress, delayed distress, rumination, urge to respond, and responsibility to do something about the NJRE, from 1 (absence) to 7 (extreme level /or within the past day).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Yale OCD Research Clinic; 1-855-623-9253; ocd.research@yale.edu

Contact: Stephen Kichuk, MPH; 203-974-7534; stephen.kichuk@yale.edu

Locations

United States, Connecticut

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

New Haven, Connecticut, United States, 06519

Contact: Stephen Kichuk, MPH 203-974-7534 stephen.kichuk@yale.edu

Contact: OCD Research 1-855-623-9253 ocd.research@yale.edu

Sponsors and Collaborators

Yale University

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Christopher Pittenger, MD, PhD; Associate Professor of Psychiatry; Director, Yale OCD Research Clinic

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT04131829
• Other Study ID Numbers: 2000023688; 1R01MH116038-01A1 ( U.S. NIH Grant/Contract ); 1K24MH121571-01 ( U.S. NIH Grant/Contract )
• First Posted: October 18, 2019
• Last Update Posted: December 7, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Obsessive-Compulsive Disorder; Mental Disorders; Anxiety Disorders; Fluoxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors