A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Sidney Kennedy, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00188942
First received: September 12, 2005
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Fluoxetine+Olanzapine
Drug: Olanzapine
Procedure: Functional Magnetic Resonance Imaging
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • 17 Item - Hamilton Depression Rating Scale - Weekly [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Clinical Global Impression - Improvement/Severity - Weekly [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Young Mania Rating Scale - Weekly [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Positive Affect Negative Affect Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Beck Depression Inventory [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • State Trait Anxiety Index [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Behavioural Activation/Inhibition Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • SexFX Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • AMDP-5 Symptom Questionnaire [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: February 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fluoxetine + Olanzapine Drug: Fluoxetine+Olanzapine Drug: Olanzapine Procedure: Functional Magnetic Resonance Imaging

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria: (All three groups)

  • 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

  • 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.

Exclusion Criteria: (All three groups)

  • 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;

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00188942

Locations
Canada, Ontario
University Health Network - Toronto Western Division
Toronto, Ontario, Canada, M5T2S8
University Health Network - Toronto General Division
Toronto, Ontario, Canada, M5G2C4
Sponsors and Collaborators
University Health Network, Toronto
Eli Lilly and Company
Investigators
Principal Investigator: Sidney H. Kennedy, MD, FRCPC University Health Network, Department of Psychiatry, University of Toronto
  More Information

Publications:
Responsible Party: Sidney Kennedy, Principal Investigator, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00188942     History of Changes
Other Study ID Numbers: UHN REB 04-0204-B, CTA Control #095694
Study First Received: September 12, 2005
Last Updated: February 6, 2013
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Magnetic Resonance Imaging
Diagnostic Imaging
Mood Disorders
Major Depressive Disorder
Antipsychotic
Olanzapine
Fluoxetine

Additional relevant MeSH terms:
Bipolar Disorder
Depressive Disorder
Depression
Depressive Disorder, Major
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Fluoxetine
Olanzapine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on September 14, 2014