fMRI Study of Treatment Changes in Major Depression | NCT01027559

NCT01027559

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
R01MH064821	U.S. NIH Grant/Contract		View source
2R01MH064821-05A2	U.S. NIH Grant/Contract		View source
DDTR A3-NSI	Other Grant/Funding Number	National Institute of Mental Health

Status Module

Name	Class
National Institute of Mental Health (NIMH)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Depressed Group: CBT	Active Comparator	Depressed participants randomized to receive Cognitive Behavioral Therapy (CBT) for treatment. A fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan will occur immediately following the completion of 12 weeks of therapy.	Behavioral: Cognitive Behavioral Therapy
Healthy Control Group	No Intervention	Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.
Depressed Group: SRT	Active Comparator	Depressed participants randomized to receive the antidepressant sertraline (SRT) for treatment. A fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan will occur immediately following the completion of 12 weeks of therapy.	Drug: Sertraline

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sertraline	Drug	Depressed participants will be randomized to SRT or CBT treatment. For those in the SRT treatment condition, visits will involve dispensing medications, checking for side effects and administering the Hamilton Depression rating scale occurring at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84. Depressed patients treated with SRT will titrate up to a maximum dose of 200 mg daily depending on tolerability and inadequate antidepressant response. Depressed subjects will start their SRT treatment once their first MRI and computer testing sessions are completed.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Blood Oxygen-level Dependent Activations During an Emotional Distractor Task Between fMRI Scans of Depressed Participants in the CBT Group and Control Participants.	MRI imaging was completed on 50 participants (26 depressed who were randomized to the CBT group and 24 controls) for this analysis, including fMRI scans to evaluate regional brain activation in depression during an emotional distractor task. Image data from their baseline visit was processed and analyzed to show differences in blood oxygen-level dependent (BOLD) activations between depressed participants in the CBT group and control participants in a priori regions (amygdala and dorsolateral prefrontal cortex) during the task. The specified regions were masked on the images, and voxel-wise comparisons (ANOVAs) were performed to determine differences in activations between groups within these masked regions Positive values reflect a BOLD activation in that region; negative reflects a BOLD de-activation in that region.	baseline visit and 8-week follow-up
Hamilton Depression Rating Scale Score at Baseline and 12 Weeks	The patient was rated by a research team member among 17 dimensions/items pertaining to depression symptoms experienced over the last week. Each item is scored from 0 (=absent), up to 2 or 4 (depending on the item). The maximum total score on the assessment, indicating the most severe depression, would be 52. A total score of 0-7 is considered to be normal. Total scores of 20 or higher indicate moderate, severe, or very severe depression. A 50% or greater drop in Hamilton Depression Rating Scale signifies response to treatment.	Baseline and 12 weeks

Eligibility Module

Eligibility Criteria

DEPRESSED GROUP:

Inclusion criteria:

Age 18-50
DSM-IV criteria for major depressive disorder (MDD)
Minimum Hamilton Rating Scale for Depression (HAMD) score > 18
Right handed
Capacity to give informed consent and follow study procedures
English speaking

Exclusion criteria:

Cannot give informed consent
Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures
Does not speak English
Known primary neurological disorders
Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic)
MRI contraindications e.g. foreign metallic implants, pacemaker
Known allergy or hypersensitivity to sertraline
Active suicidality
Severe or unstable medical illness or conditions or drugs that may cause depression
Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, psychotic features of depression, current obsessive compulsive disorder (OCD) or panic disorder. In general, subjects with a history of other Axis I disorders prior to their depression will be excluded.
Current episode has failed to respond to adequate trials of two prior antidepressants for at least 6 weeks at therapeutic doses.
Treatment with sertraline for at least one month in past 3 months.
Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics.
Current psychotherapy
Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers.

CONTROL GROUP:

Inclusion criteria:

Age 18-50
No history of MDD
HAMD score < 7
Right handed
Capacity to give informed consent and follow study procedures
English speaking

Exclusion criteria:

Cannot give informed consent
Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures
Does not speak English
Known primary neurological disorders
Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic)
MRI contraindications e.g. foreign metallic implants, pacemaker
Severe or unstable medical illness or conditions or drugs that may cause depression
Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, major depression, OCD or panic disorder.
Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics.
Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers.

Name	Affiliation	Role
Yvette I Sheline, MD	University of Pennsylvania	Principal Investigator
Charles Conway, MD	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University		St Louis	Missouri	63110	United States

Arm/Group Information

ID	Title	Description
FG000	Depressed Group: CBT	Depressed participants randomized to receive Cognitive Behavioral Therapy (CBT) for treatment. fMRI scan session occurs immediately prior to starting treatment, and a second fMRI scan will occur following 12 weeks of therapy. Cognitive Behavioral Therapy: 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 HAMD administration will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84.
FG001	Healthy Control Group	Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.
FG002	Depressed Group: Sertraline	Depressed participants randomized to receive sertraline (SRT) for treatment. fMRI scan session occurs immediately prior to starting treatment, and a second fMRI scan will occur following 12 weeks of therapy. Sertraline: Visits will involve dispensing medication, side effects assessment and HAMD administration occurring at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84. Depressed patients treated with SRT will titrate up to a maximum dose of 200 mg daily depending on tolerability and inadequate antidepressant response.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Depressed Group: CBT	Depressed participants randomized to receive Cognitive Behavioral Therapy (CBT) for treatment. fMRI scan session occurs immediately prior to starting treatment, and a second fMRI scan will occur following 12 weeks of therapy. Cognitive Behavioral Therapy: 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 HAMD administration will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Blood Oxygen-level Dependent Activations During an Emotional Distractor Task Between fMRI Scans of Depressed Participants in the CBT Group and Control Participants.	MRI imaging was completed on 50 participants (26 depressed who were randomized to the CBT group and 24 controls) for this analysis, including fMRI scans to evaluate regional brain activation in depression during an emotional distractor task. Image data from their baseline visit was processed and analyzed to show differences in blood oxygen-level dependent (BOLD) activations between depressed participants in the CBT group and control participants in a priori regions (amygdala and dorsolateral prefrontal cortex) during the task. The specified regions were masked on the images, and voxel-wise comparisons (ANOVAs) were performed to determine differences in activations between groups within these masked regions Positive values reflect a BOLD activation in that region; negative reflects a BOLD de-activation in that region.	fMRI data from a total of 26 depressed participants randomized to receive CBT and 24 control participants was analyzed. The primary aim was to compare depressed and control participants to evaluate regional brain activation during an emotional task, both at baseline and 8-week follow-up. The primary regions analyzed were the amygdala and DLPFC.	Posted		Mean	Standard Deviation	Voxels		baseline visit and 8-week follow-up

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Depressed Group: CBT	Depressed participants randomized to receive Cognitive Behavioral Therapy (CBT) for treatment. fMRI scan session occurs immediately prior to starting treatment, and a second fMRI scan will occur following 12 weeks of therapy. Cognitive Behavioral Therapy: 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 HAMD administration will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84.

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Term
D015057	1-Naphthylamine
D000588	Amines
D009930	Organic Chemicals
D009281	Naphthalenes