Major DepressionPhase 4NCT00704860
Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
A Phase 4 study testing Open label pharmacotherapy in people with Major Depression, run by University of Ottawa at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression
- What is being tested?
- Open label pharmacotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2005to Dec 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female between ages of 18 to 65 years of age.
- A diagnosis of Major Depression according to the DSM-IV criteria
- Failing to achieve remission while receiving at least two different antidepressants at adequate dosage for at least 6 weeks.
- Initial score of at least 18 on the HAMD-17 item rating scale
Who cannot join
- A diagnosis of substance abuse or dependence in the last 6 months or a lifetime diagnosis of substance abuse according to the DSM-IV criteria, elicited by inquiry.
- A diagnosis of post-traumatic stress disorder, schizophrenia, schizo-affective disorder and other psychotic disorders, anorexia nervosa or a history of a manic or mixed episode
- Major medical illnesses including endocrine and neurological disorders, as well as a history of significant head trauma
- Exposure to oral or intravenous steroids
- Contraindications to magnetic resonance imaging
- An IQ less than 80
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of Ottawa Institute of Mental Health Research
Ottawa, Ontario, K1Z 7K4
About this study
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.
Read the detailed description
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.
The investigators 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 the investigators 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.
- Conditions
- Major Depression
- Being tested
- Open label pharmacotherapy
- Keywords
- healthy volunteers treatment resistant major depression hippocampus atrophy MRI serotonin genotyping
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open label pharmacotherapyOther
Also called All classes of antidepressants, based on patient need
Dosage and drug types change based on patients need and response.
doxepin, clomipramine, amoxapine, amitriptyline, maprotiline, desipramine, nortriptyline, trimipramine, imipramine, protriptyline, isocarboxazid, phenelzine, tranylcypromine, moclobemide, fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, atomoxetine, pramipexole, bromocriptine, quetiapine, clozapine, olanzapine, ziprasidone, aripiprazole, paliperidone, Risperidone, bupropion, mirtazapine, pindolol, topiramate, trazodone, Lithium,
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Open label pharmacotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Remission from Depression and Hippocampal Atrophy
Measured: 6 months
Secondary outcomes (1)
5-HT1a Genetic Markers
Measured: Baseline Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2008 (estimated)
- Study startFeb 2005
- Primary completionNov 2009
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ottawa
- Sponsor type
- University, hospital or other
- Investigators
- Pierre M Blier, MD, Ph.D, Principal investigator, University of Ottawa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00704860
- Sponsor's protocol ID
- REB- 200506
- Status last verified
- Feb 2009
- First submitted
- 18 Jun 2008
- Last updated
- 19 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
- ClinicalTrials.gov ID
- NCT00704860
- Acronym / sponsor ID
- REB- 200506
- Conditions
- Major Depression
- Keywords
- healthy volunteers treatment resistant major depression hippocampus atrophy MRI serotonin genotyping
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of OttawaUniversity, hospital or other
- Study start
- Feb 2005
- Primary completion
- Nov 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 25 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The investigators 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 the investigators 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TR | Experimental | Other: Open label pharmacotherapyTR- 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female between ages of 18 to 65 years of age.
- A diagnosis of Major Depression according to the DSM-IV criteria
- Failing to achieve remission while receiving at least two different antidepressants at adequate dosage for at least 6 weeks.
- Initial score of at least 18 on the HAMD-17 item rating scale
Key exclusion criteria (6 listed)
- A diagnosis of substance abuse or dependence in the last 6 months or a lifetime diagnosis of substance abuse according to the DSM-IV criteria, elicited by inquiry.
- A diagnosis of post-traumatic stress disorder, schizophrenia, schizo-affective disorder and other psychotic disorders, anorexia nervosa or a history of a manic or mixed episode
- Major medical illnesses including endocrine and neurological disorders, as well as a history of significant head trauma
- Exposure to oral or intravenous steroids
- Contraindications to magnetic resonance imaging
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Open label pharmacotherapyAlso: All classes of antidepressants, based on patient needDosage and drug types change based on patients need and response. doxepin, clomipramine, amoxapine, amitriptyline, maprotiline, desipramine, nortriptyline, trimipramine, imipramine, protriptyline, isocarboxazid, phenelzine, tranylcypromine, moclobemide, fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, atomoxetine, pramipexole, bromocriptine, quetiapine, clozapine, olanzapine, ziprasidone, aripiprazole, paliperidone, Risperidone, bupropion, mirtazapine, pindolol, topiramate, trazodone, Lithium, | Other | TR |
Primary outcome
Sustained Remission from Depression and Hippocampal Atrophy
Time frame: 6 months
1 secondary outcome
5-HT1a Genetic Markers
Time frame: Baseline Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2011.
- University of Ottawa Institute of Mental Health research homepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre M Blier, MD, Ph.D principal investigator
University of Ottawa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Open label pharmacotherapy in people with Major Depression, run by University of Ottawa at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained Remission from Depression and Hippocampal Atrophy (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2011.