Traumatic Brain INjury
Conditions
Keywords
Attention, Traumatic Brain INjury, Atomoxetine, Strattera
Brief summary
Atomoxetine is the only medication that is currently approved by the FDA for the treatment of attention deficit hyperactivity disorder in adults. It has gained recent interest as an alternative medication for treating attentional problems related to traumatic brain injury (TBI), but it's effectiveness in this population has not been studied. There are a number of advantages of Atomoxetine over traditional neuro-stimulant medications currently used for attentional disorders after traumatic brain injury. This study will use a randomized double-blind placebo-controlled crossover design to investigate the efficacy of atomoxetine to improve attention, behavioral function, and depression in adults with TBI
Interventions
DRUGatomoxetine
DRUGplacebo
Sponsors
Craig Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* History of TBI * Moderate to severe TBI as indicated by Glasgow Coma Score (GCS) score of 12 or less; or Post Traumatic Amnesia (PTA) of seven days or more * at least one year post injury * between the ages of 18-65 (inclusive) * symptoms consistent with attentional dysfunction * consent to participate in study
Exclusion criteria
* history of any conditions that would prohibit standard neuropsychological testing * non-English speaking (to the extent that would limit ability to complete study measures) * prior history of significant psychiatric illness requiring hospitalization * epilepsy * cardiovascular disease or risks including: dysrhythmias, angina, myocardial infarction, uncontrolled hypertension, valvular heart disease including mitral valve prolapse * use of any monoamine oxidase inhibitor or any other drug affecting brain monoamine concentrations * severe renal or hepatic impairment * pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CDR Power of Attention | Post treatment | Cognitive Drug Research (CDR) Computerized Cognitive Assessment System \[19\] is comprised of a battery of computer-controlled tasks administered on a laptop computer with parallel forms of the tests being presented on each testing session. The Power of Attention factor of the CDR was selected as the primary outcome measure because of its strong psychometric properties in other drug studies with cognitively compromised populations. Instead of utilizing a t-test to compare treatment and control groups, treatment and control groups for both primary and secondary outcomes were compared utilizing an analysis of covariance (ANCOVA) model in which repeat baseline measures taken on each respective outcome served as a covariate. This method controls for any differences that may exist between the groups at baseline. Model assumptions for conducting an ANCOVA were investigated for all primary and secondary analyses, where no violations of model assumptions were detected. Additionally, |
| Stroop Test Interference T-score | Post treatment | The Stroop Color and Word Test is frequently used to study deficits of attention and executive function in individuals with TBI, and has adequate test-retest reliability. At each administration, the following scores were obtained, Word Reading, Colour Naming and Interference. Raw scores were converted to demographically-adjusted T-scores using Golden and Freshwater norm. |
| Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale Summary Score | Post treatment | The Adult ADHD Self-Report Scale (ASRS-v1.1) is a self-report questionnaire that consists of questions involving the 18-items of the The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV- Text Revision (TR) criteria for ADHD that rate symptoms on a Likert scale ranging from 0-4 based on the frequency of symptoms (never, rarely, sometimes, often, and very often). A previous study of the ASRS found the self-report to be both valid (Cronbach's alpha =.88) and reliable (ICC=.84). Scores on the 18 items were summed for a total ASRS score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurobehavioral Functioning Inventory Depression Subscale | Post treatment | Neurobehavioral Functioning Inventory (NFI) was developed as a clinical and research tool to quantify a variety of post-injury behaviours and symptoms characteristic of neurologic disability and encountered in daily life. The inventory is comprised of 76 items organized into six analytically derived factor scales: Depression, Somatic, Memory/Attention, Communication, Aggression, and Motor. Respondents are asked to rate items as occurring never, rarely, sometimes, often, or always. Using the standardized scoring procedures outlined in the NFI Manual, T-scores were calculated for the Depression sub-scale. Lower T-score indicates less depressive symptomotology. |
Countries
United States
Participant flow
Recruitment details
175 people responded to recruitment flier in the Denver area and were screened for eligibility from April 2008 through December 2011. 60 of these enrolled in the study.
Pre-assignment details
60 enrolled participants completed study training; 2 of these withdrew prior to Baseline Assessment. 58 completed baseline assessment and began Placebo Run-in; 3 withdrew prior to randomization. 55 total were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine 40mg atomoxetine twice a day for 2 weeks
atomoxetine : | 26 |
| Placebo Placebo twice a day for two weeks
placebo : | 29 |
| Total | 55 |
Baseline characteristics
| Characteristic | Atomoxetine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 29 Participants | 55 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 18 Participants | 23 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 29 |
| serious Total, serious adverse events | 0 / 26 | 0 / 29 |
Outcome results
Primary
Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale Summary Score
The Adult ADHD Self-Report Scale (ASRS-v1.1) is a self-report questionnaire that consists of questions involving the 18-items of the The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV- Text Revision (TR) criteria for ADHD that rate symptoms on a Likert scale ranging from 0-4 based on the frequency of symptoms (never, rarely, sometimes, often, and very often). A previous study of the ASRS found the self-report to be both valid (Cronbach's alpha =.88) and reliable (ICC=.84). Scores on the 18 items were summed for a total ASRS score.
Time frame: Post treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atomoxetine | Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale Summary Score | 28.883 units on a scale |
| Placebo | Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale Summary Score | 30.997 units on a scale |
Primary
CDR Power of Attention
Cognitive Drug Research (CDR) Computerized Cognitive Assessment System \[19\] is comprised of a battery of computer-controlled tasks administered on a laptop computer with parallel forms of the tests being presented on each testing session. The Power of Attention factor of the CDR was selected as the primary outcome measure because of its strong psychometric properties in other drug studies with cognitively compromised populations. Instead of utilizing a t-test to compare treatment and control groups, treatment and control groups for both primary and secondary outcomes were compared utilizing an analysis of covariance (ANCOVA) model in which repeat baseline measures taken on each respective outcome served as a covariate. This method controls for any differences that may exist between the groups at baseline. Model assumptions for conducting an ANCOVA were investigated for all primary and secondary analyses, where no violations of model assumptions were detected. Additionally,
Time frame: Post treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atomoxetine | CDR Power of Attention | 1262.1744 msec |
| Placebo | CDR Power of Attention | 1252.9510 msec |
Primary
Stroop Test Interference T-score
The Stroop Color and Word Test is frequently used to study deficits of attention and executive function in individuals with TBI, and has adequate test-retest reliability. At each administration, the following scores were obtained, Word Reading, Colour Naming and Interference. Raw scores were converted to demographically-adjusted T-scores using Golden and Freshwater norm.
Time frame: Post treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atomoxetine | Stroop Test Interference T-score | 56.50 T-score |
| Placebo | Stroop Test Interference T-score | 55.44 T-score |
Secondary
Neurobehavioral Functioning Inventory Depression Subscale
Neurobehavioral Functioning Inventory (NFI) was developed as a clinical and research tool to quantify a variety of post-injury behaviours and symptoms characteristic of neurologic disability and encountered in daily life. The inventory is comprised of 76 items organized into six analytically derived factor scales: Depression, Somatic, Memory/Attention, Communication, Aggression, and Motor. Respondents are asked to rate items as occurring never, rarely, sometimes, often, or always. Using the standardized scoring procedures outlined in the NFI Manual, T-scores were calculated for the Depression sub-scale. Lower T-score indicates less depressive symptomotology.
Time frame: Post treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atomoxetine | Neurobehavioral Functioning Inventory Depression Subscale | 27.53 T-score |
| Placebo | Neurobehavioral Functioning Inventory Depression Subscale | 29.47 T-score |