Traumatic Brain Injury, Attention Deficit Disorder
Conditions
Keywords
Traumatic Brain Injury, Attention Deficit, TBI
Brief summary
The purpose of this research study is to evaluate whether Vyvanse, a psychostimulant, can help with attention deficits due to traumatic brain injury (TBI). Vyvanse is currently approved for the treatment of Attention-Deficit/Hyperactivity (ADHD). The exact effects this drug may have on attention deficits caused by TBI are not known, but we expect that Vyvanse will be of some help in treating those types of problems as well. The study will utilize functional magnetic resonance imaging (fMRI) methods, as well as neurobehavioral measures, to elucidate neural mechanisms of response.
Detailed description
Symptoms of inattentiveness, impulsivity, and poor persistence have been observed in both children and adults following traumatic brain injury (TBI). These often are among the most prominent symptoms manifested and may contribute to interference in a variety of other functional domains. Although there has been some use of psychostimulant medication to treat TBI-acquired attention deficits, it remains a relatively uncommon clinical practice. This study, by highlighting mechanisms of action, could serve to promote the appropriate use of this type of treatment for the patients.
Interventions
DRUGVyvanse
30 mg - 70 mg capsules taken every morning for 6 weeks.
PROCEDUREfMRI
Brain scans (fMRI) performed at baseline, 6 week visit and 12th week visit.
DRUGPlacebo
Placebo capsules taken every morning for 6 weeks.
Sponsors
Shire
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Males and females, ages 16 to 45 * Closed head injury rated as moderate/severe (based on Glasgow Coma Scale rating, estimated posttraumatic amnesia, etc.) * Sustained 6 to 36 months earlier, and considered to be neurologically stable * Persistent (\> 6 months) problems with focused or sustained attention (+1 SD or worse on Inattention component of ADHD self ratings) corroborated by professional staff (nurses, therapists, etc.) or caregivers. Problems with attention/concentration rated as among most prominent cognitive changes. * Accompanying features may include diminished arousal/speed/stamina and/or disinhibited symptoms
Exclusion criteria
* Penetrating head injury * Pre-injury history of diagnosed ADHD * Other psychiatric conditions such as mania or psychosis. Current posttraumatic stress disorder (PTSD) symptoms may be present but not so severe as to require pharmacologic treatment. * Lifetime history of psychostimulant abuse or dependence. Other (non-psychostimulant) substance abuse within the past 6 months. Total lifetime drug use will not exceed 5 times each for substances such as amphetamine, meth-amphetamine, or cocaine. * Prior treatment with psychostimulant(s) * Tics or other contraindications for psychostimulant use including arteriosclerosis, cardiovascular disease, uncontrolled hypertension or hyperthyroidism, glaucoma, agitation, use of MAO inhibitor within 6 weeks * Current treatment with other psychotropic medication(s) within the past 6 weeks * Estimated IQ \< 80 * Sensory and/or motor impairment(s) seriously limiting testing options * Other neurological conditions including epilepsy, degenerative disorders, brain tumor, or stroke. * Physical conditions affecting arousal, activity level or stamina, including uncontrolled thyroid dysfunction, anemia, autoimmune or metabolic disorders, untreated moderate/severe sleep apnea, etc. * Persons for whom MRI scanning is contraindicated, including weight greater than 275 pounds (due to scanner table limitations), severe claustrophobia, implanted electronic medical devices (e.g. pacemaker, cochlear or other inner ear implant, deep brain stimulator), metallic foreign object in eye or rest of the body, history of sheet metal work, aneurysm clips, non-removable metallic piercings, and dental prosthetics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II) | 12 weeks | Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Hit Reaction Time (RT) Inter-Stimulus Interval (ISI) Change assesses the ability to adapt to changing inter-stimulus intervals. Inter-stimulus intervals refers to the amount of time between presentation of stimuli. High t-scores indicate that RT increased as the ISI increased; negative values indicate that RT decreased as the ISI increased. Less Hit RT ISI Change indicates less variability in RT depending on the speed of presentation. |
| Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Conners Adult ADHD Rating Scale: Long Form (CAARS:L) Inattention/Memory Problems Sub-scale. | 12 weeks | The CAARS:L is an assessment tool that prompts an observer to provide valuable information about the client. This instrument is helpful when considering a diagnosis of ADHD or related problem. High scores on the Inattention/Memory Problems sub-scale may indicate difficulty in concentration, difficulty planning or completing tasks, forgetfulness, absent-mindedness, and/or being disorganized. T-scores (M = 50, SD = 10) are used to measure ratings with higher t-scores indicating greater inattention and memory problems. When a t-score is around 60, this indicates greater risk. |
| Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials Sub-scale. | 12 weeks | The BRIEF-A is a standardized rating scale developed to observe everyday behaviors associated with specific domains of the executive functions in adults ages 18 to 90 years. The Organization of Materials scale measures orderliness of work, living, and storage spaces. T-scores (M = 50, SD = 10) are used to interpret the individual's level of executive functioning on the BRIEF-A, with higher scores indicating more difficulty in a particular area. |
| Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 12 weeks | Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Preservations represent responses in which reaction time was less than 100 ms; these responses are assumed to be anticipatory, random, or slow/inattentive (i.e., carried over from the previous response) because it is physiologically impossible to respond accurately in so short a time. Higher T-scores, percentiles, and means indicate worse performance. |
| Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Wechsler Adult Intelligence Scale -- Fourth Edition (WAIS-IV) Digit Span-Backward Subtest. | 12 weeks | Digit Span repeats strings of digits of increasing length said by the examiner in the same (forward) and in reverse (backward) order. It measures working memory and concentration with a range of scaled scores from 1-19, with higher scaled scores indicating better performance when compared to population norms. |
Secondary
| Measure | Time frame |
|---|---|
| The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response. | 12 weeks |
| Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment | 12 weeks |
Countries
United States
Participant flow
Pre-assignment details
Of the 22 cases enrolled, five were lost prior to the baseline assessment (moved, unable to contact, no-showed). Two cases were left on hold. Two cases met safety end-point criteria before group assignment. This left 13 individuals who were assigned to groups.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Drug: Vyvanse 30 mg for 7 days. 50 mg for 7 days. 70 mg for 28 days.
Procedure/Surgery: fMRI Brain scans (fMRI) performed 3 times.
Drug: Placebo Capsules taken for 42 days. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 28.85 years STANDARD_DEVIATION 8.61 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II)
Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Hit Reaction Time (RT) Inter-Stimulus Interval (ISI) Change assesses the ability to adapt to changing inter-stimulus intervals. Inter-stimulus intervals refers to the amount of time between presentation of stimuli. High t-scores indicate that RT increased as the ISI increased; negative values indicate that RT decreased as the ISI increased. Less Hit RT ISI Change indicates less variability in RT depending on the speed of presentation.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II) | 58.08 t-scores | Standard Deviation 17.92 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II) | 65.93 t-scores | Standard Deviation 17.61 |
p-value: 0.047t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).
Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Hit Reaction Time (RT) Block Change measures inattention and vigilance. Lower values indicate less slowing in RT as the test progressed. High T-scores indicate decreased vigilance over time.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 47.70 t-scores | Standard Deviation 7.47 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 54.21 t-scores | Standard Deviation 7.68 |
p-value: 0.052t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).
Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Hit Reaction Time (RT) Standard Error (SE) measures inattention. Consistency of response times is measured by the standard error for responses to targets. Higher values indicate a greater amount of inattention.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 54.26 ms | Standard Deviation 18.21 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 64.04 ms | Standard Deviation 15.68 |
p-value: 0.047t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).
Conner's Continuous Performance Task (CPT-II) measure sustained attention and response inhibition. CPT-II Preservations represent responses in which reaction time was less than 100 ms; these responses are assumed to be anticipatory, random, or slow/inattentive (i.e., carried over from the previous response) because it is physiologically impossible to respond accurately in so short a time. Higher T-scores, percentiles, and means indicate worse performance.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 50.23 ms | Standard Deviation 6.67 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). | 59.76 ms | Standard Deviation 17.29 |
p-value: 0.053t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials Sub-scale.
The BRIEF-A is a standardized rating scale developed to observe everyday behaviors associated with specific domains of the executive functions in adults ages 18 to 90 years. The Organization of Materials scale measures orderliness of work, living, and storage spaces. T-scores (M = 50, SD = 10) are used to interpret the individual's level of executive functioning on the BRIEF-A, with higher scores indicating more difficulty in a particular area.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials Sub-scale. | 48.55 t-scores | Standard Deviation 7.95 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials Sub-scale. | 56.00 t-scores | Standard Deviation 12.76 |
p-value: 0.047t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Conners Adult ADHD Rating Scale: Long Form (CAARS:L) Inattention/Memory Problems Sub-scale.
The CAARS:L is an assessment tool that prompts an observer to provide valuable information about the client. This instrument is helpful when considering a diagnosis of ADHD or related problem. High scores on the Inattention/Memory Problems sub-scale may indicate difficulty in concentration, difficulty planning or completing tasks, forgetfulness, absent-mindedness, and/or being disorganized. T-scores (M = 50, SD = 10) are used to measure ratings with higher t-scores indicating greater inattention and memory problems. When a t-score is around 60, this indicates greater risk.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Conners Adult ADHD Rating Scale: Long Form (CAARS:L) Inattention/Memory Problems Sub-scale. | 51.25 t-scores | Standard Deviation 13.29 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Conners Adult ADHD Rating Scale: Long Form (CAARS:L) Inattention/Memory Problems Sub-scale. | 56.33 t-scores | Standard Deviation 12.39 |
p-value: 0.04t-test, 2 sided
Primary
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Wechsler Adult Intelligence Scale -- Fourth Edition (WAIS-IV) Digit Span-Backward Subtest.
Digit Span repeats strings of digits of increasing length said by the examiner in the same (forward) and in reverse (backward) order. It measures working memory and concentration with a range of scaled scores from 1-19, with higher scaled scores indicating better performance when compared to population norms.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Wechsler Adult Intelligence Scale -- Fourth Edition (WAIS-IV) Digit Span-Backward Subtest. | 11.60 units on a scale | Standard Deviation 3.86 |
| Placebo | Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using the Wechsler Adult Intelligence Scale -- Fourth Edition (WAIS-IV) Digit Span-Backward Subtest. | 9.40 units on a scale | Standard Deviation 4.4 |
p-value: 0.003t-test, 2 sided
Secondary
Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment
Time frame: 12 weeks
Population: No data were collected.
Secondary
The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response.
Time frame: 12 weeks
Population: Based on the analysis of neurobehavioral assessment data, complications with screening, and limited sample size, the neural mechanisms of response to Vyvanse vs placebo were not significant enough to be measured and compared by fMRI. There is no data from the fMRI to be reported because it was abandoned as an aspect of this study before analysis.