Major Depressive DisorderPhase 4NCT00188942
A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder
A Phase 4 study testing Fluoxetine+Olanzapine, Olanzapine and Functional Magnetic Resonance Imaging in people with Major Depressive Disorder, run by University Health Network, Toronto at 2 sites in Canada.
Trial summary
This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Fluoxetine+Olanzapine, Olanzapine and Functional Magnetic Resonance Imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2005to Jun 2009
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- age 18-55 years
- satisfactory physical health
- education level and a degree of understanding to communicate effectively with the investigator c
- capable of providing informed consent
- female subjects of childbearing potential, a medically accepted means of contraception.
- Additional inclusion criteria for the patient groups include
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- DSM-IV-TR criteria for a diagnosis of BD or MDD
- currently meeting criteria for an MDE and
- a Hamilton Depression Rating Scale 17 Item (HDRS-17) score of > 17
- blood indices within normal clinical ranges.
Who cannot join
- DSM-IV-TR criteria for substance abuse or dependence (except nicotine or caffeine) within the past 6 months
- comorbid neurological or other major psychiatric disorders as defined in the DSM-IV-TR;
- history of neurological trauma resulting in loss of consciousness;
- uncorrected hypothyroidism or hyperthyroidism, including elevated thyroid stimulating hormone (TSH);
- other unstable medical condition;
- female subjects who are pregnant or nursing;
Show all 14Show fewer
- Additional exclusion criteria for the BD and MDD group include:
- prior failure to respond to fluoxetine and olanzapine in combination at adequate dose and duration;
- evidence of serious risk of suicide based on clinician assessment and/or HRSD suicide item > 3;
- course of ECT (electroconvulsive therapy) in the preceding 6 months;
- Young Mania Rating Scale (YMRS) > 7;
- administration of fluoxetine within previous 4 weeks;
- treatment resistance as defined by the failure of two antidepressant trials from dissimilar classes
- Hyperglycemia or diabetes mellitus as defined by a fasting blood glucose value of > 125 mg/dl.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
University Health Network - Toronto General Division
Toronto, Ontario, M5G2C4
University Health Network - Toronto Western Division
Toronto, Ontario, M5T2S8
About this study
Official title: Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation
This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Depressed patients will be treated with a combination of fluoxetine and olanzapine and undergo MRI scans before, during, and after pharmacotherapy.
Read the detailed description
The purpose of this study is to further characterize the neural correlates of affective processing in BD and MDD subjects using fMRI. Subjects who meet criteria for a major depressive episode in the context of BD (n=15); MDD (n=15) and a group of psychiatrically unaffected control subjects (CS, n=15) will undergo four fMRI scans while experiencing a temporary mood induction through the presentation of affective imagery from the International Affective Picture System (IAPS). Both BD and MDD subjects will receive the same combination pharmacotherapy to treat the depression, with fMRI data acquired before, and 1, 3, 6 weeks following pharmacotherapy initiation. Positive, negative, and neutral affective visual stimuli will be presented in a blocked design.
Comparison(s): The effects of time and group will be analyzed in factorial models. Regions of interest that demonstrate significant group-by-time interactions will be further correlated with self-report and clinician-rated psychometric indices.
- Conditions
- Major Depressive Disorder
- Being tested
- Fluoxetine+Olanzapine, Olanzapine, Functional Magnetic Resonance Imaging
- Keywords
- Magnetic Resonance Imaging, Diagnostic Imaging, Mood Disorders, Major Depressive Disorder, Antipsychotic, Olanzapine, Fluoxetine
- Medical subject headings
- Depressive Disorder, Major, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluoxetine+OlanzapineDrug
OlanzapineDrug
Functional Magnetic Resonance ImagingProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Fluoxetine + Olanzapine | Active comparator | Not described Receives: Drug: Fluoxetine+Olanzapine; Drug: Olanzapine; Procedure: Functional Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.
Measured: 6 weeks
17 Item - Hamilton Depression Rating Scale - Weekly
Measured: 6 weeks
Clinical Global Impression - Improvement/Severity - Weekly
Measured: 6 weeks
Young Mania Rating Scale - Weekly
Measured: 6 weeks
Secondary outcomes (6)
Positive Affect Negative Affect Scale
Measured: 6 weeks
Beck Depression Inventory
Measured: 6 weeks
State Trait Anxiety Index
Measured: 6 weeks
Behavioural Activation/Inhibition Scale
Measured: 6 weeks
SexFX Scale
Measured: 6 weeks
AMDP-5 Symptom Questionnaire
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startFeb 2005
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Sidney Kennedy, University Health Network, Toronto
- Investigators
- Sidney H. Kennedy, MD, FRCPC, Principal investigator, University Health Network, Department of Psychiatry, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00188942
- Sponsor's protocol ID
- UHN REB 04-0204-B
- Other IDs
- CTA Control #095694
- Status last verified
- Feb 2013
- First submitted
- 12 Sep 2005
- Last updated
- 8 Feb 2013
- Results posted
- No
Publications
Kumari V, Mitterschiffthaler MT, Teasdale JD, Malhi GS, Brown RG, Giampietro V, Brammer MJ, Poon L, Simmons A, Williams SC, Checkley SA, Sharma T. Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biol Psychiatry. 2003 Oct 15;54(8):777-91. doi: 10.1016/s0006-3223(02)01785-7.
PubMed 14550677Malhi GS, Lagopoulos J, Ward PB, Kumari V, Mitchell PB, Parker GB, Ivanovski B, Sachdev P. Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci. 2004 Feb;19(3):741-54. doi: 10.1111/j.0953-816x.2003.03159.x.
PubMed 14984424Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003 Jan;160(1):64-75. doi: 10.1176/appi.ajp.160.1.64.
PubMed 12505803
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation
- ClinicalTrials.gov ID
- NCT00188942
- Acronym / sponsor ID
- UHN REB 04-0204-B
- Conditions
- Major Depressive Disorder
- Keywords
- Magnetic Resonance Imaging, Diagnostic Imaging, Mood Disorders, Major Depressive Disorder, Antipsychotic, Olanzapine, Fluoxetine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- Feb 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 16 Sep 2005 (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.
This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Depressed patients will be treated with a combination of fluoxetine and olanzapine and undergo MRI scans before, during, and after pharmacotherapy.
Detailed description
The purpose of this study is to further characterize the neural correlates of affective processing in BD and MDD subjects using fMRI. Subjects who meet criteria for a major depressive episode in the context of BD (n=15); MDD (n=15) and a group of psychiatrically unaffected control subjects (CS, n=15) will undergo four fMRI scans while experiencing a temporary mood induction through the presentation of affective imagery from the International Affective Picture System (IAPS). Both BD and MDD subjects will receive the same combination pharmacotherapy to treat the depression, with fMRI data acquired before, and 1, 3, 6 weeks following pharmacotherapy initiation. Positive, negative, and neutral affective visual stimuli will be presented in a blocked design.
Comparison(s): The effects of time and group will be analyzed in factorial models. Regions of interest that demonstrate significant group-by-time interactions will be further correlated with self-report and clinician-rated psychometric indices.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fluoxetine + Olanzapine | Active comparator | Drug: Fluoxetine+Olanzapine, Drug: Olanzapine, Procedure: Functional Magnetic Resonance Imaging |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- age 18-55 years
- satisfactory physical health
- education level and a degree of understanding to communicate effectively with the investigator c
- capable of providing informed consent
- female subjects of childbearing potential, a medically accepted means of contraception.
Key exclusion criteria (14 listed)
- DSM-IV-TR criteria for substance abuse or dependence (except nicotine or caffeine) within the past 6 months
- comorbid neurological or other major psychiatric disorders as defined in the DSM-IV-TR;
- history of neurological trauma resulting in loss of consciousness;
- uncorrected hypothyroidism or hyperthyroidism, including elevated thyroid stimulating hormone (TSH);
- other unstable medical condition;
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 |
|---|---|---|
| Fluoxetine+Olanzapine | Drug | Fluoxetine + Olanzapine |
| Olanzapine | Drug | Fluoxetine + Olanzapine |
| Functional Magnetic Resonance Imaging | Procedure or surgery | Fluoxetine + Olanzapine |
Primary outcome
MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.
Time frame: 6 weeks
17 Item - Hamilton Depression Rating Scale - Weekly
Time frame: 6 weeks
Clinical Global Impression - Improvement/Severity - Weekly
Time frame: 6 weeks
Young Mania Rating Scale - Weekly
Time frame: 6 weeks
6 secondary outcomes
Positive Affect Negative Affect Scale
Time frame: 6 weeks
Beck Depression Inventory
Time frame: 6 weeks
State Trait Anxiety Index
Time frame: 6 weeks
Behavioural Activation/Inhibition Scale
Time frame: 6 weeks
SexFX Scale
Time frame: 6 weeks
AMDP-5 Symptom Questionnaire
Time frame: 6 weeks
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 8 Feb 2013.
- Background: PubMed 14550677Kumari V, Mitterschiffthaler MT, Teasdale JD, Malhi GS, Brown RG, Giampietro V, Brammer MJ, Poon L, Simmons A, Williams SC, Checkley SA, Sharma T. Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biol Psychiatry. 2003 Oct 15;54(8):777-91. doi: 10.1016/s0006-3223(02)01785-7.
- Background: PubMed 14984424Malhi GS, Lagopoulos J, Ward PB, Kumari V, Mitchell PB, Parker GB, Ivanovski B, Sachdev P. Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci. 2004 Feb;19(3):741-54. doi: 10.1111/j.0953-816x.2003.03159.x.
- Background: PubMed 12505803Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003 Jan;160(1):64-75. doi: 10.1176/appi.ajp.160.1.64.
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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.
Sidney H. Kennedy, MD, FRCPC principal investigator
University Health Network, Department of Psychiatry, University of Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluoxetine+Olanzapine, Olanzapine and Functional Magnetic Resonance Imaging in people with Major Depressive Disorder, run by University Health Network, Toronto at 2 sites 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 10 inclusion and 14 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 8 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy. (time frame: 6 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00188942, which also lists 3 linked publications.
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 8 Feb 2013.