The Gut Microbiota in Obsessive-Compulsive Disorder
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional

Summary: 
      This study will examine the gut microbiota and serum inflammatory markers in patients with
      Obsessive-Compulsive Disorder vs. healthy controls. Phase II of the study will examine the
      gut microbiota and cytokine levels following 12-weeks of treatment with Selective Serotonin
      Reuptake Inhibitors (SSRIs).
    

Detailed description: 
      Phase I of the study will involve 25 healthy controls (no anxiety or mood disorders) and 25
      outpatients with primary DSM 5 OCD. Participants ages 18-65 will be assessed using the Mini
      International Neuropsychiatric Interview (MINI) to determine whether criteria for a primary
      OCD diagnosis is met alongside any additional comorbid disorders. Healthy controls will also
      be assessed using the MINI to confirm the absence of any psychiatric disorders. Participants
      will complete a number of clinician and self-rated symptom severity scales as listed below:

      a. Yale Brown Obsessive-Compulsive Scale (YBOCS) - Clinician-rated b. Montgomery Asberg
      Depression Rating Scale (MADRS) - Clinician-rated c. Obsessive-Compulsive Inventory - Revised
      (OCI-R) - Self-rated d. Depression Anxiety Stress Scale (DASS-21) - Self-rated e. Dutch
      Dimensional Obsessive-Compulsive Scale (DDOCS) - Self-rated

      2. They will also complete additional questionnaires pertaining to their diet and bowel
      functioning:

        1. Gastrointestinal Symptom Rating Scale (GSRS)

        2. Short-form Leeds Dyspepsia Questionnaire (SF-LDQ)

        3. Rome III criteria for Irritable Bowel Syndrome

        4. Assessment of diet using the Anti-Cancer Council of Victoria Food Frequency
           Questionnaire (ACCVFFQ).

           3. Subjects will also be asked to provide background information regarding travel in the
           past 4 months and current place (and duration) of residence as these factors may
           potentially affect the microbiome profile.

           4. Patients will be weighed and their height measured to determine body mass index
           (BMI).

           5. Those who meet study criteria will be provided with a collection kit and instructed
           on appropriate fecal sample collection. The sample should be the first bowel movement of
           the day. Participants will have a blood sample drawn to examine serum levels of IL-6,
           TNF- α and CRP.

      Fecal Sample Collection Patients and healthy controls will collect fecal samples at home
      using the investigators well-established protocol. Stool samples will be collected and
      transferred to a sterile screw capped sample jar and placed in a standard household freezer.
      The samples will be transported on the cooling pad to study personnel at the MacAnxiety
      Research Centre where they will be stored in a study freezer before transport to McMaster
      University. In the laboratory, part of the stool sample will be transferred into four 2-ml
      cryovials and snap frozen using liquid nitrogen for molecular analysis of microbiota.

      PHASE II:

      Participants interested in pharmacological treatment for their OCD symptoms after completing
      phase 1, will have the option to continue into phase 2 of the study. Here participants will
      receive 12-weeks of standard open-label treatment with an SSRI. During this 12 week period,
      subjects will attend 5 additional visits. The first 3 visits will occur once every 2 weeks
      while visits 4 and 5 will occur at weeks 8 and 12 of treatment. As per the APA guidelines
      (APA 2007) participants will receive 4-6 weeks of treatment at the optimal dosage.

      The visits will be organized as follows:

        1. Baseline Visit: This visit will correspond with the procedures outlined in Part One of
           the study. Participants will also begin open-label SSRI treatment at this visit, once
           blood and stool samples have been collected. In this Phase the clinician will also
           complete the following scales at each visit:

           i. Clinical Global Impression - Improvement (CGI-I) - Clinician-rated ii. Clinical
           Global Impression - Severity (CGI-S) - Clinician-rated

        2. During each visit (visits 2-5) participants will be assessed by the treating physician
           to determine whether modifications to SSRI dosage are warranted. Dosage increases will
           be based on response to present dose and experienced side effects. The clinician-rated
           Y-BOCS and MADRS will also be completed at each visit. Patients will complete the
           ACCVFFQ at visit 3 (week 4). The medication dosage will not be increased after visit 5.

        3. Visit 6 (week 12): Participants will undergo usual assessment, treatment response will
           also be determined at this visit (CGI-I score ≤ 2 as well as a 30% drop in YBOCS score).
           Participants will be provided with a collection kit and instructed on appropriate fecal
           sample collection (as outlined above). The sample collected will be the first bowel
           movement of the day. Blood samples will be drawn at a local Gamma-Dynacare lab to
           examine serum levels of IL-6, TNF α and CRP. Patient diet will also be assessed using
           the ACCVFFQ.

        4. After returning the fecal sample and completing the bloodwork, participants will begin a
           2-week taper period where the subject will be instructed to gradually reduce the dosage
           of the prescribed SSRI. Participants will have the option to continue treatment in the
           situation where they wish to do so.
    

Intervention name(s): SSRIs
Intervention type(s): Drug
Intervention description(s): 12-weeks of standard SSRi treatment for those interested in Phase II of the study.
Other intervention name(s): Fluoxetine; Paroxetine; Fluvoxamine; Escitalopram; Citalopram; Sertraline
Intervention MeSH terms: Fluvoxamine; Citalopram; Fluoxetine; Paroxetine; Sertraline; Escitalopram
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Selective Serotonin Reuptake Inhibitors