Traumatic Brain InjuryPhase 3NCT01000064
Treatment of Traumatic Brain Injury (TBI)-Related Attention Deficits
A Phase 3 study testing Vyvanse and fMRI in people with Traumatic Brain Injury and Attention Deficit Disorder, run by Vanderbilt University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 45 years
- Conditions the study is for
- Traumatic Brain Injury, Attention Deficit Disorder
- What is being tested?
- Vyvanse and fMRI
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to May 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Psychostimulant Treatment of TBI-Related Attention Deficits: fMRI Analysis of Neural Mechanisms of Response
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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Attention Deficit Disorder
- Being tested
- Vyvanse, fMRI, Placebo
- Keywords
- Traumatic Brain Injury, Attention Deficit, TBI
- Medical subject headings
- Brain Injuries, Traumatic, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VyvanseDrug
30 mg - 70 mg capsules taken every morning for 6 weeks.
fMRIProcedure or surgery
Also called functional magnetic resonance imaging
Brain scans (fMRI) performed at baseline, 6 week visit and 12th week visit.
PlaceboDrug
Placebo capsules taken every morning for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vyvanse; Procedure: fMRI; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 weeks
Secondary outcomes (2)
Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment
Measured: 12 weeks
The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionDec 2013
- Study completionMay 2015
Why it stopped: unable to meet recruitment goals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- Shire
- Responsible party
- Principal investigator, Michael G. Tramontana, Vanderbilt University
- Investigators
- Michael G Tramontana, Ph.D., Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01000064
- Sponsor's protocol ID
- TBI 090563
- Status last verified
- Apr 2017
- First submitted
- 15 Oct 2009
- Last updated
- 19 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychostimulant Treatment of TBI-Related Attention Deficits: fMRI Analysis of Neural Mechanisms of Response
- ClinicalTrials.gov ID
- NCT01000064
- Acronym / sponsor ID
- TBI 090563
- Conditions
- Traumatic Brain Injury, Attention Deficit Disorder
- Keywords
- Traumatic Brain Injury, Attention Deficit, TBI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: unable to meet recruitment goals
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- Shire
- Study start
- Oct 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 22 Oct 2009 (estimated)
- Results
- Posted 19 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vyvanse | Active comparator | Drug: Vyvanse, Procedure: fMRI, Drug: PlaceboVyvanse 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. |
| Placebo | Placebo comparator | Drug: Vyvanse, Procedure: fMRI, Drug: PlaceboVyvanse 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. |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vyvanse30 mg - 70 mg capsules taken every morning for 6 weeks. | Drug | Placebo, Vyvanse |
| fMRIAlso: functional magnetic resonance imagingBrain scans (fMRI) performed at baseline, 6 week visit and 12th week visit. | Procedure or surgery | Placebo, Vyvanse |
| PlaceboPlacebo capsules taken every morning for 6 weeks. | Drug | Placebo, Vyvanse |
Primary outcome
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).
Time frame: 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 Conners Continuous Performance Task (CPT-II).
Time frame: 12 weeks
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.
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II)
Time frame: 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 Conners Continuous Performance Task (CPT-II).
Time frame: 12 weeks
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.
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.
Time frame: 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.
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.
Time frame: 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.
Time frame: 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.
2 secondary outcomes
Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment
Time frame: 12 weeks
The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response.
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael G Tramontana, Ph.D. principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vyvanse and fMRI in people with Traumatic Brain Injury and Attention Deficit Disorder, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II). (time frame: 12 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2017.