Predicting Medication Response in Obsessive Compulsive Disorder

This study has been completed.
Sponsor:
Collaborators:
Obsessive Compulsive Foundation
Centre for Addiction and Mental Health
Information provided by (Responsible Party):
Dr. Peggy Richter, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT01404871
First received: February 6, 2009
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

In this study, the investigators hope to study a number of variables the investigators believe may help us predict why some people respond better to some medications than others. Participants will be randomly assigned to receive one of two typical medications for OCD, clomipramine or escitalopram. Individuals who would like to participate but who have previously tried one or both of these medications may instead take a newer drug, duloxetine, and undergo the identical procedures. The factors the investigators will be studying include demographics (i.e. age, gender, age of onset of OCD), genetic markers (such as variants in genes involved in breaking down drugs in the liver (cytochrome P450 system), and genes involved in several brain chemical systems, such as serotonin), the dimensions of OCD symptoms (i.e. checking, washing, and hoarding) and cortical inhibition. Cortical inhibition will be measured transcranial magnetic stimulation and is being studied because deficits in this process may be important in the development of OCD. The investigators hypothesize that certain pretreatment clinical characteristics will correlate with poor treatment response including earlier age of onset, longer duration of illness, increased YBOCS severity and presence of significant hoarding symptoms. The investigators expect that increasing degree of deficit in CI pre-treatment will predict poor treatment response, but that increase in CI from pre- to post-treatment will correlate with a positive treatment response. Differences in genetic marker status for cytochrome P450 genes will correlate with tolerability and/or response, as well as differences in genetic marker status in SLC1A1, GRIN2B, 5HT1B and 5HT2A will correlate with response.


Condition Intervention
Obsessive Compulsive Disorder
Drug: clomipramine
Drug: escitalopram
Drug: duloxetine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Official Title: Predicting Medication Response in Obsessive Compulsive Disorder

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • YBOCS Obsessive-Compulsive Severity Score [ Time Frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks) ] [ Designated as safety issue: No ]
    The YBOCS yields an OCD severity score by scoring participants on time, interference, distress, resistance and control of their obsessive and compulsive symptoms on a scale of 0-4. When these scores are summed, they give a total severity score from 0-40. The primary outcome will measure the degree of change in this measurement from pre- to post-treatment.

  • Clinical Global Improvement - Improvement Scale [ Time Frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks) ] [ Designated as safety issue: No ]
    This is a clinician/Research assistant rated score of clinical improvement. Both treating physician and research assistant (who interviews the participant every two weeks) will independently provide ratings from 1-7, 1 being very much improved and 7 being very much worse.


Secondary Outcome Measures:
  • Change in cortical Inhibition (CI) as measured with Transcranial Magnetic Stimulation. [ Time Frame: Pre- and post-treatment (typically, 0 weeks and 12 weeks) ] [ Designated as safety issue: No ]
  • Genotype marker data for SLC1A1, GRIN2B, 5HT1B, 5HT2A and P450 enzymes CYP2D6 and CYP2C19. [ Time Frame: Collected at week 0, analyzed periodically (approx. 1x/year) ] [ Designated as safety issue: No ]
    We will initially focus on GLU and GABA gene candidates for which there is good evidence of involvement in cortical inhibition. We will also prioritize other markers previously implicated in response and/or etiology of the illness including 5HT1B, 5HT2A, 5HTT, DRD3, DRD4, MOG, BDNF, MAOA, COMT. We will test 200 SNPs across these 12 genes, and also explore any highly promising genes emerging from the literature as time and resources permit. We will test both single markers and haplotypes. Genotyping of CYP2D6 and CYP2C19 will be typed by the Roche Diagnostics Amplichip (www.amplichip.us).

  • Tolerability/side effects measure with Udvalg for Liniske Undersogelser Side Effect Rating Scale (UKU). [ Time Frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks) ] [ Designated as safety issue: Yes ]
  • Clinical Global Impression - Severity Scale. [ Time Frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks) ] [ Designated as safety issue: No ]
  • Depression symptoms will be rated with the Beck Depression Inventory (BDI). [ Time Frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks) ] [ Designated as safety issue: No ]
  • DYBOCS (Dimensional Yale-Brown Obsessive-Compulsive Scale) [ Time Frame: start, middle and end of trial (typically, 0, 6 and 12 weeks) ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: April 2009
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Randomization to ECIT or CMI
Randomized trial of clomipramine or escitalopram
Drug: clomipramine
oral tablets, starting at 50mg/daily for 12 weeks including > 8 weeks at 250 mg/daily
Other Name: Anafranil
Drug: escitalopram
oral tablet, starting 10mg/daily 12 week treatment including >8 weeks at max dose 50mg daily
Other Name: Cipralex
Active Comparator: Open label Duloxetine
Open label trial of duloxetine
Drug: duloxetine
oral tablets, starting dose 30mg daily 12 week treatment including >8weeks at 120mg daily
Other Name: Cymbalta

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of Obsessive Compulsive Disorder
  • Must be able to swallow tablets

Exclusion Criteria:

  • History of stroke
  • History of Parkinson's disease
  • History of Epilepsy
  • Clinical diagnosis of Schizophrenia or schizoaffective disorder
  • Clinical diagnosis of Bipolar Affective disorder
  • Active suicidality
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01404871

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
The Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Obsessive Compulsive Foundation
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Peggy MA Richter, MD FRCPC Sunnybrok Health Sciences Centre; Centre for Addiction and Mental Health; University of Toronto
  More Information

No publications provided

Responsible Party: Dr. Peggy Richter, Director, Clinic for OCD & Related Disorders Head, Frederick W. Thompson Anxiety Disorders Centre Dept. of Psychiatry, Sunnybrook Health Sciences Centre Associate Professor of Psychiatry, University of Toronto, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT01404871     History of Changes
Other Study ID Numbers: OCF-Richter
Study First Received: February 6, 2009
Last Updated: January 30, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Sunnybrook Health Sciences Centre:
OCD
pharmacogenetics
cortical inhibition
genetics

Additional relevant MeSH terms:
Obsessive-Compulsive Disorder
Compulsive Personality Disorder
Anxiety Disorders
Mental Disorders
Personality Disorders
Clomipramine
Citalopram
Duloxetine
Dexetimide
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Antidepressive Agents, Second-Generation

ClinicalTrials.gov processed this record on July 26, 2014