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fMRI Study of Treatment Changes in Major Depression

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ClinicalTrials.gov Identifier: NCT01027559
Recruitment Status : Completed
First Posted : December 8, 2009
Results First Posted : June 13, 2018
Last Update Posted : July 17, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Other
Conditions Major Depression
Treatment
Interventions Drug: Sertraline
Behavioral: Cognitive Behavioral Therapy
Enrollment 97

Recruitment Details  
Pre-assignment Details Prior to being assigned to a group, 6 depressed participants dropped from the study before being assigned to treatment type.
Arm/Group Title Depressed Group: CBT Healthy Control Group Depressed Group: Sertraline
Hide Arm/Group Description

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.

Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.

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.

Period Title: Overall Study
Started 26 34 31
Completed 20 26 22
Not Completed 6 8 9
Arm/Group Title Depressed Group: CBT Depressed Group: SRT Healthy Control Group Total
Hide Arm/Group Description

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.

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.

Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after. Total of all reporting groups
Overall Number of Baseline Participants 26 31 34 91
Hide Baseline Analysis Population Description
A total of 97 participants enrolled in the study (63 depressed and 34 controls). Of the 63 depressed participants enrolled in the study, 57 (26 CBT and 31 SRT) were assigned to a treatment group and completed at least some study-related activities. Six depressed participants dropped from the study before being assigned to treatment type.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 26 participants 31 participants 34 participants 91 participants
31.54
(18 to 48)
33.29
(19 to 49)
31.64
(18 to 48)
32.16
(18 to 49)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 31 participants 34 participants 91 participants
Female 19 26 28 77
Male 7 5 5 19
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 26 participants 31 participants 34 participants 91 participants
26 31 34 91
1.Primary Outcome
Title Blood Oxygen-level Dependent Activations During an Emotional Distractor Task Between fMRI Scans of Depressed Participants in the CBT Group and Control Participants.
Hide Description 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.
Time Frame baseline visit and 8-week follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Depressed Group Healthy Control Group
Hide Arm/Group Description:

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.

Cognitive Behavioral Therapy: Depressed participants will be randomized to SRT or CBT treatment. For those in the CBT 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. Depressed subjects will start their CBT treatment once their first MRI and computer testing sessions are completed.

Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.
Overall Number of Participants Analyzed 26 24
Mean (Standard Deviation)
Unit of Measure: Voxels
Amygdala - baseline -18.74  (98.45) 2.71  (141.09)
DLPFC - baseline 316.24  (199.83) 411.2  (241.53)
Amygdala - Time 2 -16.82  (108.55) -46.06  (97.10)
DLPFC - Time 2 403.72  (248.02) 421.51  (231.33)
2.Primary Outcome
Title Hamilton Depression Rating Scale Score at Baseline and 12 Weeks
Hide Description 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.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Numbers may differ from Participant Flow but these are the totals of those participants who had data at this time point for the Hamilton Depression Rating Scale.
Arm/Group Title Depressed Group: CBT Healthy Control Group Depressed Group: Sertraline
Hide Arm/Group Description:

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.

Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.

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 Hamilton Depression Rating Scale (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.

Overall Number of Participants Analyzed 18 15 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 19.94  (5.23) 1.38  (1.33) 20.79  (3.98)
Week 12 5.94  (6.08) 1.07  (1.33) 4.43  (5.37)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Depressed Group: CBT Healthy Control Group Depressed Group: SSRI (Selective Serotonin Re-Uptake Inhibitor
Hide Arm/Group Description

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.

Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.

Depressed participants randomized to receive setraline (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.

All-Cause Mortality
Depressed Group: CBT Healthy Control Group Depressed Group: SSRI (Selective Serotonin Re-Uptake Inhibitor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Depressed Group: CBT Healthy Control Group Depressed Group: SSRI (Selective Serotonin Re-Uptake Inhibitor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/34 (0.00%)   0/31 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Depressed Group: CBT Healthy Control Group Depressed Group: SSRI (Selective Serotonin Re-Uptake Inhibitor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/26 (26.92%)   2/34 (5.88%)   21/31 (67.74%) 
Cardiac disorders       
Tachycardia/Palpitations  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Ear and labyrinth disorders       
Dizziness/Faintness  1/26 (3.85%)  0/34 (0.00%)  8/31 (25.81%) 
Difficulty Hearing/Tinnitus  0/26 (0.00%)  0/34 (0.00%)  3/31 (9.68%) 
Eye disorders       
Blurred Vision  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Gastrointestinal disorders       
Constipation  2/26 (7.69%)  0/34 (0.00%)  6/31 (19.35%) 
Nausea/Vomitting  3/26 (11.54%)  0/34 (0.00%)  10/31 (32.26%) 
Stomach/Abdominal Pain  2/26 (7.69%)  0/34 (0.00%)  5/31 (16.13%) 
Diarrhea  1/26 (3.85%)  0/34 (0.00%)  5/31 (16.13%) 
General disorders       
Increased Salivation  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Weight Loss  0/26 (0.00%)  0/34 (0.00%)  3/31 (9.68%) 
Immune system disorders       
Dry Mouth  3/26 (11.54%)  0/34 (0.00%)  10/31 (32.26%) 
Malaise  2/26 (7.69%)  0/34 (0.00%)  5/31 (16.13%) 
Nasal Congestion  2/26 (7.69%)  0/34 (0.00%)  8/31 (25.81%) 
Musculoskeletal and connective tissue disorders       
Back Pain [1]  2/26 (7.69%)  2/34 (5.88%)  1/31 (3.23%) 
Abnormal Muscle Tone/Movements  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Nervous system disorders       
Sedation/Drowsiness  4/26 (15.38%)  0/34 (0.00%)  17/31 (54.84%) 
Excitement/Weakness  3/26 (11.54%)  0/34 (0.00%)  5/31 (16.13%) 
Headache  3/26 (11.54%)  0/34 (0.00%)  12/31 (38.71%) 
Irritability  5/26 (19.23%)  0/34 (0.00%)  8/31 (25.81%) 
Muscle Twitching  1/26 (3.85%)  0/34 (0.00%)  8/31 (25.81%) 
Tremor  1/26 (3.85%)  0/34 (0.00%)  4/31 (12.90%) 
Decreased Appetite  2/26 (7.69%)  0/34 (0.00%)  8/31 (25.81%) 
Increased Appetite  2/26 (7.69%)  0/34 (0.00%)  5/31 (16.13%) 
Weight Gain  2/26 (7.69%)  0/34 (0.00%)  5/31 (16.13%) 
Insomnia  1/26 (3.85%)  0/34 (0.00%)  7/31 (22.58%) 
Decreased Libido  2/26 (7.69%)  0/34 (0.00%)  7/31 (22.58%) 
Impaired Mentation  2/26 (7.69%)  0/34 (0.00%)  4/31 (12.90%) 
Sexual Dysfunction  0/26 (0.00%)  0/34 (0.00%)  6/31 (19.35%) 
Excessive Sweating  2/26 (7.69%)  0/34 (0.00%)  4/31 (12.90%) 
Slurred Speech  2/26 (7.69%)  0/34 (0.00%)  1/31 (3.23%) 
Psychiatric disorders       
Panic  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Reproductive system and breast disorders       
Menstrual Irregularity  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Respiratory, thoracic and mediastinal disorders       
Hyperventilation  1/26 (3.85%)  0/34 (0.00%)  4/31 (12.90%) 
Vascular disorders       
Chest Pain  1/26 (3.85%)  0/34 (0.00%)  2/31 (6.45%) 
Increased Libido  0/26 (0.00%)  0/34 (0.00%)  3/31 (9.68%) 
Syncope  0/26 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
[1]
Back pain/stiffness from taking part in the MRI scan
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Yvette Sheline
Organization: University of Pennsylvania
Phone: 215-573-0082
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01027559     History of Changes
Other Study ID Numbers: 081348
R01MH064821 ( U.S. NIH Grant/Contract )
2R01MH064821-05A2 ( U.S. NIH Grant/Contract )
DDTR A3-NSI ( Other Grant/Funding Number: National Institute of Mental Health )
First Submitted: December 4, 2009
First Posted: December 8, 2009
Results First Submitted: June 15, 2016
Results First Posted: June 13, 2018
Last Update Posted: July 17, 2018