Clinical trial NCT04131829: Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD
Official title: Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2019-10-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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.

Primary outcomes:
measure: Obsessive-compulsive severity change
timeFrame: 18 weeks
Secondary outcomes:
measure: Tic severity change
timeFrame: 18 weeks
measure: Beck Depression Inventory-II
timeFrame: 18 weeks
measure: Anxiety
timeFrame: 18 weeks
measure: Obsessive-compulsive concerns
timeFrame: 18 weeks
measure: Magical ideation
timeFrame: 18 weeks
measure: Sensory phenomena
timeFrame: 18 weeks
measure: "Not Just Right" experiences and sensations in OCD
timeFrame: 18 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale OCD Research Clinic - CMHC/CNRU, 34 Park ST
state: Connecticut
Study officials:
affiliation: Professor of Psychiatry; Director, Yale OCD Research Clinic
name: Christopher Pittenger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: