Trial Outcomes & Findings for Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury (NCT NCT00704379)
NCT ID: NCT00704379
Last Updated: 2015-08-25
Results Overview
Following the DSM-IV (now updated by the DSM-5), depressive disorders associated with TBI are categorized as Mood Disorder Due to Another Medical Condition with subtypes: 1) With major depressive-like episode (if the full criteria for a major depressive episode \[MDE\] are met) or 2) With depressive features (prominent depressed mood but full criteria for a MDE are not met); and 3) with mixed features (e.g. significant irritability, pressured speech and formal thought disorder). On the other hand, bipolar and related disorders due to TBI are subdivided in: 1) with manic or hypomanic like episode; 2) with manic features; and 3) with mixed features. A similar conceptual framework has been used to define Anxiety Disorder due to another Medical Condition, in this case, TBI. According to DSM-IV/DSM-5, such diagnosis can be made when, besides an evident pathophysiological relationship with TBI, panic attacks or generalized anxiety are the prominent features of the clinical presentation.
COMPLETED
PHASE2/PHASE3
94 participants
6 months after TBI
2015-08-25
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
48
|
|
Overall Study
COMPLETED
|
39
|
41
|
|
Overall Study
NOT COMPLETED
|
7
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury
Baseline characteristics by cohort
| Measure |
Placebo
n=46 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=48 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
Total
n=94 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.91 years
STANDARD_DEVIATION 18.24 • n=5 Participants
|
49.98 years
STANDARD_DEVIATION 20.05 • n=7 Participants
|
52.39 years
STANDARD_DEVIATION 19.24 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 months after TBIFollowing the DSM-IV (now updated by the DSM-5), depressive disorders associated with TBI are categorized as Mood Disorder Due to Another Medical Condition with subtypes: 1) With major depressive-like episode (if the full criteria for a major depressive episode \[MDE\] are met) or 2) With depressive features (prominent depressed mood but full criteria for a MDE are not met); and 3) with mixed features (e.g. significant irritability, pressured speech and formal thought disorder). On the other hand, bipolar and related disorders due to TBI are subdivided in: 1) with manic or hypomanic like episode; 2) with manic features; and 3) with mixed features. A similar conceptual framework has been used to define Anxiety Disorder due to another Medical Condition, in this case, TBI. According to DSM-IV/DSM-5, such diagnosis can be made when, besides an evident pathophysiological relationship with TBI, panic attacks or generalized anxiety are the prominent features of the clinical presentation.
Outcome measures
| Measure |
Placebo
n=46 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=48 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Time to Onset of Diagnostic and Statistical Manual (DSM) IV Defined Mood and Anxiety Disorders Associated With Traumatic Brain Injury (TBI)
|
21.4264 weeks
Standard Error 0.9982
|
15.7833 weeks
Standard Error 0.2091
|
SECONDARY outcome
Timeframe: 6 months after TBIPopulation: Out of the 80 participants who completed the trial, only 68 completed CIQ at this evaluation time.
The Community Integration Questionnaire (CIQ) is intended as a brief, reliable measure of an individual's level of integration into the home and community following traumatic brain injury. Total CIQ scores were used as the outcome measure. Range: 0 to 25. Higher scores indicate higher levels of integration into the home and community following TBI.
Outcome measures
| Measure |
Placebo
n=30 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=38 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Total Community Integration Questionnaire Scores
|
16.77 units on a scale
Standard Deviation 3.69
|
17.67 units on a scale
Standard Deviation 4.37
|
SECONDARY outcome
Timeframe: 6 months after TBIPopulation: Out of the 80 participants who completed the trial, only 64 completed IGT at this evaluation time.
The Iowa Gambling Task (IGT) evaluates decision making ability. During IGT subjects have to choose between decks of cards which yield high immediate gain but larger future loss (i.e., long term loss), and decks which yield lower immediate gain but a smaller future loss (i.e., a long term gain). The task consists of four decks of cards: A, B, C, and D. The goal in the task is to maximize profit. Subjects are required to make a series of card selections. The decks A and B are long term loss decks and the decks C and D are long term gain decks. The IGT Score reported is the combination of the raw score for each deck combined in the following way: (C+D) - (A+B). The range for this score is: -100 to 100. Higher values of this score indicate better decision making ability.
Outcome measures
| Measure |
Placebo
n=33 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=31 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Iowa Gambling Task Score
|
16.67 units on a scale
Standard Deviation 29
|
-0.77 units on a scale
Standard Deviation 28
|
SECONDARY outcome
Timeframe: 6 months following traumatic brain injuryPopulation: Out of the 80 participants who completed the trial, only 61 completed all the tests necessary to calculate the composite score at this evaluation time.
This outcome measures memory function and is a composite of five standardized scores: Brief Visuospatial Memory Test - Revised, Delayed Recall and California Verbal Learning Test, Short Delay Free Recall Number Correct and Discriminability, and Long Delay Free Recall Number Correct and Discriminability. Standardized scores (i.e., z-scores) for each test of this composite were obtained by subtracting the mean raw score of all participants to the raw score of each participant and dividing the result by the standard deviation of the raw scores of all participants. The composite score was obtained by averaging the z-scores of the four memory tests mentioned previously. Range: -3 to 3. Higher scores represent better memory function.
Outcome measures
| Measure |
Placebo
n=29 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=32 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Memory Function Composite
|
-0.08 z-scores
Standard Deviation 0.75
|
0.07 z-scores
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: 6 months after TBIPopulation: Out of the 80 participants who completed the trial, only 63 completed SFE at this evaluation time.
The Social Functioning Examination (SFE) is a semi-structured interview that measures social functioning in areas such as interpersonal relationships, work adjustment, use of community resources and satisfaction with living environment. Range: 0 to 1. Higher scores denote lower levels of social functioning.
Outcome measures
| Measure |
Placebo
n=29 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=34 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Social Functioning Examination Total Score
|
0.04 units on a scale
Standard Deviation 0.04
|
0.04 units on a scale
Standard Deviation 0.06
|
SECONDARY outcome
Timeframe: BaselinePopulation: Of the 94 participants randomized, only 61 participants had an MRI and were included in the analysis of this study aim.
FA is a measured obtained from Diffusion Tensor Imaging, an image modality of Magnetic Resonance Imaging (MRI). FA is a unitless index. Range: 0 to 1. FA describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is unrestricted or equally restricted in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. In the context of this study, FA measures the integrity of the cingulate gyrus white matter. Higher FA values reflect higher integrity of the cingulate gyrus white matter tract. Average FA values for the right and left cingulate gyri were summed. One aim of this project was to identify predictors of the occurrence of mood disturbances during the first 6 months following TBI. The hypothesis for this aim was that patients who develop a mood or anxiety disorder six months after TBI present at baseline with lower FA of the cingulate gyrus than those who do not.
Outcome measures
| Measure |
Placebo
n=8 Participants
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=53 Participants
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Neuroimaging Variables (i.e., Fractional Anisotropy [FA] of Frontal White Matter Such as the Cingulate Gyrus)
|
0.91 unitless index
Standard Deviation 0.06
|
0.94 unitless index
Standard Deviation 0.07
|
Adverse Events
Placebo
Sertraline
Serious adverse events
| Measure |
Placebo
n=46 participants at risk
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=48 participants at risk
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Hip fracture
|
2.2%
1/46
|
2.1%
1/48
|
Other adverse events
| Measure |
Placebo
n=46 participants at risk
Placebo (i.e., an inactive substance) was given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
|
Sertraline
n=48 participants at risk
Sertraline (other name: Zoloft) was administered in a double blind fashion via tablets administered once daily. Targeted dosage: 100 mg/day.
|
|---|---|---|
|
General disorders
Diarrhea
|
15.2%
7/46
|
31.2%
15/48
|
|
General disorders
Dizziness
|
19.6%
9/46
|
25.0%
12/48
|
|
General disorders
Dry mouth
|
4.3%
2/46
|
25.0%
12/48
|
|
General disorders
Fatigue
|
2.2%
1/46
|
6.2%
3/48
|
|
General disorders
Insomnia
|
13.0%
6/46
|
6.2%
3/48
|
|
General disorders
Lightheadedness
|
15.2%
7/46
|
16.7%
8/48
|
|
General disorders
Nausea
|
6.5%
3/46
|
6.2%
3/48
|
|
General disorders
Sweating
|
0.00%
0/46
|
6.2%
3/48
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place