Treatment of Traumatic Brain Injury (TBI)-Related Attention Deficits

Study Overview
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Brief Summary
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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
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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.

Official Title
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Psychostimulant Treatment of TBI-Related Attention Deficits: fMRI Analysis of Neural Mechanisms of Response

Conditions
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Traumatic Brain Injury, Attention Deficit Disorder

Intervention / Treatment
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* Drug: Vyvanse
* Procedure: fMRI
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vyvanse<br>Vyvanse capsule, 30-70 mg, each morning for 6 weeks. Placebo capsule each morning for 6 weeks. Brain scans (fMRI) performed at baseline, 6th week visit and 12th week visit. | Drug: Vyvanse<br>* 30 mg - 70 mg capsules taken every morning for 6 weeks.<br>Procedure: fMRI<br>* Brain scans (fMRI) performed at baseline, 6 week visit and 12th week visit.<br>* Other names: functional magnetic resonance imaging;Drug: Placebo<br>* Placebo capsules taken every morning for 6 weeks.<br>|
| Placebo Comparator: Placebo<br>Vyvanse capsule, 30-70 mg, each morning for 6 weeks. Placebo capsule each morning for 6 weeks. Brain scans (fMRI) performed at baseline, 6th week visit and 12th week visit. | Drug: Vyvanse<br>* 30 mg - 70 mg capsules taken every morning for 6 weeks.<br>Procedure: fMRI<br>* Brain scans (fMRI) performed at baseline, 6 week visit and 12th week visit.<br>* Other names: functional magnetic resonance imaging;Drug: Placebo<br>* Placebo capsules taken every morning for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment |  | 12 weeks | 
| The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response. |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic Brain Injury, Attention Deficit, TBI