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Completed

NCT Number: NCT01404871

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Clomipramine

Drug

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

Other names: Anafranil

Escitalopram

Drug

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

Other names: Cipralex

Duloxetine

Drug

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

Other names: Cymbalta

Primary outcomes

  1. YBOCS Obsessive-Compulsive Severity Score

    Time frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)

    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.

  2. Clinical Global Improvement - Improvement Scale

    Time frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)

    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 outcomes

  1. Change in cortical Inhibition (CI) as measured with Transcranial Magnetic Stimulation.

    Time frame: Pre- and post-treatment (typically, 0 weeks and 12 weeks)

  2. 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)

    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).

  3. 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)

  4. Clinical Global Impression - Severity Scale.

    Time frame: Bi-monthly (every 2 weeks for duration of trial. Approx. 12 weeks)

  5. 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)

  6. DYBOCS (Dimensional Yale-Brown Obsessive-Compulsive Scale)

    Time frame: start, middle and end of trial (typically, 0, 6 and 12 weeks)

Sponsors and collaborators

Lead sponsor

Sunnybrook Health Sciences Centre

Other

Collaborators

  • Centre for Addiction and Mental Health
  • Obsessive Compulsive Foundation

Registry information

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Jul 28, 2011
Registry last updated
Jan 31, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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