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| Sponsored by: |
University of Ottawa |
|---|---|
| Information provided by: | University of Ottawa |
| ClinicalTrials.gov Identifier: | NCT00704860 |
Purpose
Reduction of volume of the hippocampus has been associated with major depression in many studies. It has been suggested that antidepressants may protect against hippocampus volume loss in humans associated with multiple episodes of depression and may also reverse the reduction of volume caused by the depression. In addition, genetic markers for serotonin are implicated with depression, and may be an indication of reduced response to antidepressant treatments.
This study aims to enroll patients who are defined as having treatment resistant depression (no remission after at least 2 treatments trials with an antidepressant). They will receive an MRI scan at the initial visit and either 6 months after sustained remission or 12 months after they enter the study for non-remitters. They will also be asked to give a blood sample for genotyping. They will be matched by age and handedness to healthy volunteers with no personal history of depression who will also receive an MRI scan and genotyping.
The first aim is to compare hippocampal volume of depressed subjects to healthy controls. It is anticipated that subjects will initially have smaller hippocampal volume but of those who sustain remission, there will be a small increase in hippocampal volume. It is also anticipated that specific genetic markers will be related to individuals response to antidepressant treatments.
| Condition | Intervention | Phase |
|---|---|---|
|
Major Depression |
Drug: Open label drug treatment |
Phase IV |
| Study Type: | Interventional |
| Study Design: | Treatment, Open Label, Single Group Assignment, Efficacy Study |
| Official Title: | Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism |
| Estimated Enrollment: | 27 |
| Study Start Date: | February 2005 |
| Estimated Study Completion Date: | December 2008 |
| Estimated Primary Completion Date: | October 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
TR: Experimental
TR- Subjects defined as having treatment resistant depression, who have failed at least 2 adequate trials of an antidepressant. Subjects will be treated in an open label trial for their depression, with the goal of sustained remission.
|
Drug: Open label drug treatment
Dosage and drug types change based on patients need and response. doxepin, clomipramine, amoxapine, amitriptyline, maprotiline, desipramine, nortriptyline, dexepin, trimipramine, imipramine, protriptyline, isocarboxazid, phenelzine, tranylcypromine, maclobemide, fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, atomoxetine, pramipexole, bromocriptine, quetiapine, clozapine, olanzapine, ziprasidone, aripiprazole, paliperidone, Risperidone, bupropion, mitrazapine, pindolol, topiramate, trazodone, Lithium, |
Individuals who are defined as having treatment-resistant major depression (failure of at least 2 trials of an antidepressant at an adequate dose) and currently meet DSM-IV criteria for depression qualify for this study. At the initial visit, each subject is given an MRI in order to perform a volumetric analysis of their hippocampus and a blood sample is taken in order to determine their genotype for the 5-HT1a(serotonin) promoter. Each patient is then aggressively treated (open label) for depression with the goal of remission. A second MRI scan is completed 6 months after sustained remission or 12 months from baseline if remission is not met or sustained.
We will select healthy volunteer controls with no personal or first relative history of depression and match with the subjects based on age and handedness. Genotyping and and MRI scan will be performed on the healthy subjects in order to compare all parameters.
Hypothesis: It is anticipated that the hippocampal volume will be smaller than those of matched controls. It is also anticipated that the Homozygous G(-1019) genotype will be more prevalent in the patient group than in the healthy subjects.
In addition, it is hypothesized that we should find a small increase in hippocampal volume after long-term treatment. Also, most non-responders will be of homozygous G(-1019) 5-HT1a genotype and will have the greatest degree of hippocampal atrophy. Moreover, it is hypothesized that patients carrying a long allele of 5-HTTLPR polymorphism for 5-HTT might show a better response to antidepressants in general. Finally, it is anticipated that the TPH*A variant of the gene coding for tryptophan hydroxylase will be associated with poorer outcome.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Chantal Hebert, R.N. | 613-722-6521 ext 6217 | chantal.hebert@rohcg.on.ca |
| Contact: Lisa Batten, MA | 613-722-6521 ext 6971 | lisa.batten@rohcg.on.ca |
| Canada, Ontario | |
| University of Ottawa Institute of Mental Health Research | Recruiting |
| Ottawa, Ontario, Canada, K1Z 7K4 | |
| Contact: Chantal Hebert, RN 6137226521 ext 6217 chantal.hebert@rohcg.on.ca | |
| Contact: Lisa Batten, MA 613-722-6521 ext 6971 lisa.batten@rohcg.on.ca | |
| Principal Investigator: Pierre M Blier, MD, Ph.D. | |
| Principal Investigator: | Pierre M Blier, MD, Ph.D | University of Ottawa Institute of Mental Health Research |
More Information
| Responsible Party: | University of Ottawa Institute of Mental Health Research ( Pierre Blier, MD, Ph.D. ) |
| Study ID Numbers: | REB- 200506 |
| Study First Received: | June 18, 2008 |
| Last Updated: | June 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00704860 History of Changes |
| Health Authority: | Canada: Health Canada |
|
healthy volunteers treatment resistant major depression hippocampus atrophy MRI serotonin genotyping |
|
Pathological Conditions, Anatomical Neurotransmitter Agents Fluvoxamine Trazodone Olanzapine Atomoxetine 9-hydroxy-risperidone Healthy Depressive Disorder, Major Desipramine Tranylcypromine Paroxetine Pramipexol Imipramine Protriptyline |
Mental Disorders Nortriptyline Venlafaxine Doxepin Sertraline Topiramate Aripiprazole Dexetimide Lithium Bromocriptine Depression Clomipramine Risperidone Lithium Carbonate Depressive Disorder |
|
Pathological Conditions, Anatomical Neurotransmitter Agents Depression Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Depressive Disorder, Major Depressive Disorder |
Serotonin Pharmacologic Actions Behavioral Symptoms Serotonin Agents Mental Disorders Mood Disorders Atrophy |
