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

NCT01000064 | Terminated Phase 3 Results

• 1 other identifier: TBI 090563
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury; Attention Deficit Disorder

Keywords

Traumatic Brain Injury; Attention Deficit; TBI

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (2)

• 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

Study Arms (2)

Vyvanse

ACTIVE COMPARATOR

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; Procedure: fMRI; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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; Procedure: fMRI; Drug: Placebo

Interventions

Vyvanse DRUG

30 mg - 70 mg capsules taken every morning for 6 weeks.

Placebo; Vyvanse

fMRI PROCEDURE

Brain scans (fMRI) performed at baseline, 6 week visit and 12th week visit.

Also known as: functional magnetic resonance imaging

Placebo; Vyvanse

Placebo DRUG

Placebo capsules taken every morning for 6 weeks.

Placebo; Vyvanse

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University: lead
• Shire: collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Attention Deficit Disorder with Hyperactivity

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Limitations and Caveats

Participant withdrawal during study leading to small numbers of participants analyzed.

Results Point of Contact

• Title: Dr. Michael G. Tramontana
• Organization: Vanderbilt University Medical Center

Michael.Tramontana@Vanderbilt.Edu

615-327-7144

Study Officials

• Michael G Tramontana, Ph.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry, Neurology, and Pediatrics

Study Record Dates

• First Submitted: October 15, 2009
• First Posted: October 22, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2015
• Last Updated: May 19, 2017
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Locations

US (1)