fMRI Study of Treatment Changes in Major Depression - Full Text View

Purpose

The overall purposes of this research are to determine if Cognitive Behavioral Therapy (CBT) has the same healing effect on the brain for people with depression as traditional anti-depressants do, to find out more about the causes of depression and why people differ in the extent of problems caused by depression, and to determine if certain differences in genes within populations are related to clinical symptoms. We hypothesize that CBT will have the same healing effect on the brain as antidepressants; that differences in brain activations created by the various tasks and genetic differences will help us understand differences in the type and severity of symptoms among the depressed subjects.

Condition	Intervention
Major Depression Treatment	Drug: Sertraline Behavioral: Cognitive Behavioral Therapy

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor)
Official Title:	fMRI Studies of Emotional Circuitry in Major Depression: Treatment Changes

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Depression Nuclear Scans

Drug Information available for: Sertraline hydrochloride Sertraline

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

Activation differences between pre- and post-treatment fMRI scans. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
A 50% or greater drop in Hamilton Depression Rating Scale signifies response to treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	February 2009
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Sertraline For those in the Sertraline treatment condition, visits to dispense medications, check for side effects and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Their first fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan session will occur immediately following the completion of 12 weeks of antidepressant therapy.	Drug: Sertraline For those in the Sertraline treatment condition, visits to dispense medications, check for side effects and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Depressed patients will be treated with Sertraline starting with a dose of 50 mg daily on Day 1 of the study. For patients showing inadequate evidence of antidepressant response, the Sertraline dose will be increased up to a maximum dose of 200 mg daily. The daily Sertraline dose can be decreased in 50 mg increments, or as clinically indicated, in the presence of side effects until two weeks prior to the end of the study. No further changes in dose will be permitted in study subjects after the 10th week until the study is completed.
Active Comparator: Cognitive Behavioral Therapy For those in the Cognitive Behavioral Therapy treatment condition, visits for the CBT sessions will occur on or about Day = 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, and Day 84. Visits to check for progress and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Their first fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan session will occur immediately following the completion of 12 weeks of CBT.	Behavioral: Cognitive Behavioral Therapy For those in the Cognitive Behavioral Therapy treatment condition, visits for the CBT sessions will occur on or about Day = 3,Day = 7,Day = 10,Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, and Day 84. Visits to check for progress and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Depressed subjects will start their CBT treatment once their first MRI and computer testing sessions are completed, and will have two sessions per week for the first two weeks, followed by one session per week for the duration of the twelve week study.

Arms

Assigned Interventions

Active Comparator: Sertraline

For those in the Sertraline treatment condition, visits to dispense medications, check for side effects and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Their first fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan session will occur immediately following the completion of 12 weeks of antidepressant therapy.

Drug: Sertraline

For those in the Sertraline treatment condition, visits to dispense medications, check for side effects and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Depressed patients will be treated with Sertraline starting with a dose of 50 mg daily on Day 1 of the study. For patients showing inadequate evidence of antidepressant response, the Sertraline dose will be increased up to a maximum dose of 200 mg daily. The daily Sertraline dose can be decreased in 50 mg increments, or as clinically indicated, in the presence of side effects until two weeks prior to the end of the study. No further changes in dose will be permitted in study subjects after the 10th week until the study is completed.

Active Comparator: Cognitive Behavioral Therapy

For those in the Cognitive Behavioral Therapy treatment condition, visits for the CBT sessions will occur on or about Day = 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, and Day 84. Visits to check for progress and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Their first fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan session will occur immediately following the completion of 12 weeks of CBT.

Behavioral: Cognitive Behavioral Therapy

For those in the Cognitive Behavioral Therapy treatment condition, visits for the CBT sessions will occur on or about Day = 3,Day = 7,Day = 10,Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, and Day 84. Visits to check for progress and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84 in depressed subjects. Depressed subjects will start their CBT treatment once their first MRI and computer testing sessions are completed, and will have two sessions per week for the first two weeks, followed by one session per week for the duration of the twelve week study.

Detailed Description:

The overall purposes of this research are to determine if Cognitive Behavioral Therapy (CBT) has the same healing effect on the brain for people with depression as traditional anti-depressants do, to find out more about the causes of depression and why people differ in the extent of problems caused by depression, and to determine if certain differences in genes within populations are related to clinical symptoms.The genes we are examining for this study are called "COMT, BDNF, and 5-HTT long arm and short arm", as well as future genes that may be discovered to play a role in depression at a later time, and will be determined by examining a sample of your saliva and a small blood sample. The method we are using to study depression is Functional Magnetic Resonance Imaging (fMRI) which takes pictures of the brain. This method allows us to identify certain parts of the brain that show how the brain works in controlling negative feelings. These pictures will compare 50 depressed individuals with 50 individuals who are not depressed.

Three tasks will be performed during the scan which are designed to cause activations in the brain areas we are interested in. In the first task, subjects will do a matching task in which the stimuli to match are either faces or houses and in which flanking distracters are either faces or houses. The goal of participants in this task is to attend to stimuli in either the horizontal or the vertical plane. On each trial, non-task relevant stimuli (distracters) are presented in the non-attended plane. One some trials these distracter stimuli are houses, on some trials neutral faces and on some trials they are negative faces. In the second task, participants will be presented with pre-recorded statements using words from the list of 555 personality/trait words compiled by Anderson (1968). Examples of these statements are "I am happy", "You are lucky", "You are dull", and "You are greedy". For negative statements, participants will be instructed to either passively listen to the statement or decrease their emotional response to the statement. For neutral statements, participants will be asked to passively listen to the statements.Subjects will then be asked how much the statement applies to them, on a 4-part Likert-type scale. In the third task, subjects will be asked to focus all their attention on a single fixation point. This will allow us to measure their resting state connectivity between specific brain regions.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age 18-50, male or female, any race
DSM-IV criteria for MDD
Minimum HAMD score > 18
Right handed
Capacity to give informed consent and follow study procedures
English speaking

Exclusion Criteria:

Significant handicaps (e.g. uncorrected visual or hearing loss, mental retardation) that would interfere with testing procedures
MRI contraindications e.g. foreign metallic implants, pacemaker
Current diagnosis of another DSM-IV disorder, such as schizophrenia or bipolar disorder, which would affect data collected for this study
Known primary neurological disorders including dementia, stroke, encephalopathy Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder.
Severe or unstable medical illness (e.g. MI within past 3 months, end stage cancer) or conditions or drugs that may cause depression (e.g. systemic steroids, uncorrected hypothyroidism)
Active suicidality
Known allergy or hypersensitivity to sertraline
Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers. No subjects will be included in the study unless they have been off all antidepressants for at least 5 drug half lives.
Does not speak English
Not right handed
History of alcoholism.
Current use of illicit drugs that may compromise the brain imaging required for this study, such as cocaine and methamphetamine, or past history of drug abuse or dependence
Any other factor that in the investigators judgement may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic)
Cannot give informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01027559

Contacts

Contact: Tony J Durbin, MA

(314) 362-7962

tonyd@npg.wustl.edu

Locations

United States, Missouri
Washington University	Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Yvette I Sheline, MD
Sub-Investigator: Charles Conway, MD

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Yvette I Sheline, MD

Washington University School of Medicine

More Information

No publications provided

Responsible Party:	Yvette Sheline, Yvette Sheline MD, Washington University, National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT01027559 History of Changes
Other Study ID Numbers:	081348, R01MH064821, 2R01MH064821-05A2, DDTR A3-NSI
Study First Received:	December 4, 2009
Last Updated:	March 27, 2013
Health Authority:	United States: Federal Government

Keywords provided by Washington University School of Medicine:

Major Depression
Functional Magnetic Resonance Imaging
Emotional Circuitry
Cognitive Behavioral Therapy

Additional relevant MeSH terms:

Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Sertraline
Psychotropic Drugs

Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 18, 2013