Predicting Medication Response in Obsessive Compulsive Disorder

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.

Study Overview

• Status: Completed
• Conditions: Obsessive Compulsive Disorder
• Intervention / Treatment: Drug: clomipramine; Drug: escitalopram; Drug: duloxetine

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5T 1R8
      • The Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Anafranil; Drug: escitalopram; oral tablet, starting 10mg/daily 12 week treatment including >8 weeks at max dose 50mg daily; Other Names: 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 Names: Cymbalta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
YBOCS Obsessive-Compulsive Severity Score	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.	Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)
Clinical Global Improvement - Improvement Scale	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.	Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cortical Inhibition (CI) as measured with Transcranial Magnetic Stimulation.		Pre- and post-treatment (typically, 0 weeks and 12 weeks)
Genotype marker data for SLC1A1, GRIN2B, 5HT1B, 5HT2A and P450 enzymes CYP2D6 and CYP2C19.	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).	Collected at week 0, analyzed periodically (approx. 1x/year)
Tolerability/side effects measure with Udvalg for Liniske Undersogelser Side Effect Rating Scale (UKU).		Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)
Clinical Global Impression - Severity Scale.		Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)
Depression symptoms will be rated with the Beck Depression Inventory (BDI).		Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)
DYBOCS (Dimensional Yale-Brown Obsessive-Compulsive Scale)		start, middle and end of trial (typically, 0, 6 and 12 weeks)

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 28, 2011

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: OCD; pharmacogenetics; cortical inhibition; genetics
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Antidepressive Agents, Tricyclic; Duloxetine Hydrochloride; Citalopram; Clomipramine
• Other Study ID Numbers: OCF-Richter

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No