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

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Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Vyvanse

fMRI

Placebo

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Traumatic Brain Injury, Attention Deficit, TBI

Eligibility Criteria

16 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Vanderbilt University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Vyvanse

Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment

The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response.

Full Information

NCT ID

NCT01000064

First Posted

October 15, 2009

Last Updated

April 10, 2017

Sponsor

Vanderbilt University

Collaborators

Shire

1. Study Identification

Unique Protocol Identification Number

NCT01000064

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Terminated

Why Stopped

unable to meet recruitment goals

Study Start Date

October 2009 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University

Collaborators

Shire

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury, Attention Deficit Disorder

Keywords

Traumatic Brain Injury, Attention Deficit, TBI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vyvanse

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Vyvanse

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

fMRI

Other Intervention Name(s)

functional magnetic resonance imaging

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo capsules taken every morning for 6 weeks.

Primary Outcome Measure Information:

Title

Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).

Description

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

Title

Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).

Description

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

Title

Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II)

Description

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

Title

Assessment of Various Components of Attention, Related Cognitive Processes and ADHD Symptoms, Using Conners Continuous Performance Task (CPT-II).

Description

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

Title

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.

Description

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

Title

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.

Description

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

Title

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.

Description

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

Secondary Outcome Measure Information:

Title

Evaluation of Which Types of Patients Are Most Likely to Benefit From Treatment

Time Frame

12 weeks

Title

The Study Will Utilize fMRI Methods (as Well as Aforementioned Neurobehavioral Measures) to Elucidate Neural Mechanisms of Response.

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael G Tramontana, Ph.D.

Organizational Affiliation

Vanderbilt University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Traumatic Brain Injury, Attention Deficit Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial