Predicting Medication Response in Obsessive Compulsive Disorder

NCT01404871 | Completed

• 1 other identifier: OCF-Richter
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Obsessive Compulsive Disorder

Keywords

OCD; pharmacogenetics; cortical inhibition; genetics

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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.

  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)

Study Arms (2)

Randomization to ECIT or CMI

ACTIVE COMPARATOR

Randomized trial of clomipramine or escitalopram

Drug: clomipramine; Drug: escitalopram

Open label Duloxetine

ACTIVE COMPARATOR

Open label trial of duloxetine

Drug: duloxetine

Interventions

clomipramine DRUG

oral tablets, starting at 50mg/daily for 12 weeks including \> 8 weeks at 250 mg/daily

Also known as: Anafranil

Randomization to ECIT or CMI

escitalopram DRUG

oral tablet, starting 10mg/daily 12 week treatment including \>8 weeks at max dose 50mg daily

Also known as: Cipralex

Randomization to ECIT or CMI

duloxetine DRUG

oral tablets, starting dose 30mg daily 12 week treatment including \>8weeks at 120mg daily

Also known as: Cymbalta

Open label Duloxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Obsessive Compulsive Foundation: collaborator
• Centre for Addiction and Mental Health: collaborator

Study Sites (2)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

The Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Clomipramine; Escitalopram; Dexetimide; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Thiophenes; Sulfur Compounds

Study Officials

• Peggy MA Richter, MD FRCPC

  Sunnybrok Health Sciences Centre; Centre for Addiction and Mental Health; University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: July 28, 2011
• Study Start: April 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 31, 2013

Record last verified: 2013-01

Locations

CA (2)