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

NCT02712996 | Completed Phase 4 Results FDA Drug

• 1 other identifier: TBI 56592
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to evaluate whether Vyvanse, a psychostimulant, can help children ages 6-16 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 adults with attention deficits caused by TBI have been investigated prior. The exact effects this drug may have on children with attention deficits caused by TBI are not known, but the investigators expect that Vyvanse will be of some help in treating this population as well.

Conditions

Traumatic Brain Injury; Attention Deficit Disorder

Keywords

Traumatic Brain Injury; Attention Deficit; TBI; Vyvanse

Outcome Measures

Primary Outcomes (17)

• Assessing Severity of Symptoms Associated With Attention-deficit/Hyperactivity Disorder (ADHD) in Children When Using Vyvanse Versus Placebo by Administering the Conners-3 Parent Form

  The Conners-3 Parent Form is used to obtain the parent's observations about behavior in their child aged 6 to 18 years old. Parents rate the child's behavior on 45 items as not true at all (0) to very much true (3). The lowest scale score is 0 (better behavior) and the highest is 135 (worse behavior). The Conners 3-P includes content Scales of Inattention, Hyperactivity/Impulsivity, Learning Problems, Executive Functioning, Aggression, and Peer/Family Relations. Inattention scale was reported as the Primary Outcome. All scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Behavior Rating Inventory of Executive Function (BRIEF) - PARENT

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). GEC was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Inattentiveness in Children Using Vyvanse Versus Placebo by Measuring Omissions on the Conners Continuous Performance Task (CPT-II).

  Conner's Continuous Performance Task (CPT-II) measures sustained attention and response inhibition. During the CPT-II, letters were presented serially on a screen in a random order. All letters were considered target stimuli, except for the letter 'X' which is a non-target stimulus. Participants responded to target stimuli by pressing the space bar of a computer keyboard (90% of the stimuli) while withholding responses to non-target stimuli (10% of the test). Omission errors represented the number of times a participant fails to respond to target letters (all other than 'X'). Raw scores were converted to z-scores (M=0, SD=+/-1). Higher scores indicate greater inattentiveness.

  12 weeks

• Assessing Physical Symptoms in Children Using Vyvanse Versus Placebo by Measuring Anxiety on the Revised Child Manifest Anxiety Scale (RCMAS)

  RCMAS is a self-report, 37-item questionnaire in which children agree (yes = 1) or disagree (no =0) to statements about themselves. A Total Anxiety score is computed based on 28 items, which are divided into 3 anxiety subscales: physiological anxiety (10 items), worry/oversensitivity (11 items), and social concerns/concentration (7 items). The remaining nine items on the RCMAS constitute the Lie (social desirability) subscale. The lowest scale score is 0 and the highest is 37. Raw scores were converted to z-scores (M=0, SD=+/-1). Because scores are derived from affirmative responses, a high score indicates a high level of anxiety or lie on that subscale.

  12 weeks

• Assessing Total Symptoms in Children Using Vyvanse Versus Placebo by Measuring Anxiety on the Revised Child Manifest Anxiety Scale (RCMAS)

  RCMAS is a self-report, 37-item questionnaire in which children agree (yes = 1) or disagree (no =0) to statements about themselves. A Total Anxiety score is computed based on 28 items, which are divided into 3 anxiety subscales: physiological anxiety (10 items), worry/oversensitivity (11 items), and social concerns/concentration (7 items). The remaining nine items on the RCMAS constitute the Lie (social desirability) subscale. The lowest scale score is 0 and the highest is 37. Raw scores were converted to z-scores (M=0, SD=+/-1). Because scores are derived from affirmative responses, a high score indicates a high level of anxiety or lie on that subscale.

  12 weeks

• Assessing Attention Problems in Children Using Vyvanse Versus Placebo by Measuring Symptoms on the Child Behavior Checklist (CBCL)

  The Child Behavior Checklist (CBCL) is a widely used caregiver report form identifying problem behavior in children. The patient is rated on 113 items scored on a 3-point Likert scale (0=not true; 1=somewhat/sometimes true; 2=very true/often true). CBCL consists of eight empirically-based syndrome subscales. The range of subscale scores (summed) are: Aggressive Behavior (0-36), Anxious/Depressed (0-26), Attention Problems (0-20), Rule-Breaking Behavior (0-34), Somatic Complaints (0-22), Social Problems (0-22), Thought Problems (0-30), and Withdrawn/Depressed (0-16). Raw scores were converted to z-scores (M=0, SD=+/-1). Higher scores indicate more severe symptoms.

  12 weeks

• Assessing Anxiety-Depression Problems in Children Using Vyvanse Versus Placebo by Measuring Symptoms on the Child Behavior Checklist (CBCL)

  The Child Behavior Checklist (CBCL) is a widely used caregiver report form identifying problem behavior in children. The patient is rated on 113 items scored on a 3-point Likert scale (0=not true; 1=somewhat/sometimes true; 2=very true/often true). CBCL consists of eight empirically-based syndrome subscales. The range of subscale scores (summed) are: Aggressive Behavior (0-36), Anxious/Depressed (0-26), Attention Problems (0-20), Rule-Breaking Behavior (0-34), Somatic Complaints (0-22), Social Problems (0-22), Thought Problems (0-30), and Withdrawn/Depressed (0-16). Raw scores were converted to z-scores (M=0, SD=+/-1). Higher scores indicate more severe symptoms.

  12 weeks

• Assessing Inhibitory Control in Children When Using Vyvanse Versus Placebo Utilizing the Inhibit Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Inhibit was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Ability to Tolerate Change in Children When Using Vyvanse Versus Placebo by Utilizing the Shift Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Shift was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Ability to Begin Tasks in Children When Using Vyvanse Versus Placebo by Utilizing the Initiate Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Initiate was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Representational Memory in Children When Using Vyvanse Versus Placebo by Utilizing the Working Memory Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Working Memory was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Task-oriented Monitoring in Children When Using Vyvanse Versus Placebo by Utilizing the Monitor Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Monitor was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Behavior Regulation in Children When Using Vyvanse Versus Placebo by Measuring the Behavior Regulation Index (BRI) on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Behavior Regulation was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Cognitive Regulation in Children When Using Vyvanse Versus Placebo by Measuring the Cognitive Regulation Index (CRI) on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Cognitive Regulation was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Emotion Regulation in Children When Using Vyvanse Versus Placebo by Measuring the Emotion Regulation Index (ERI) on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS

  The BRIEF Parent Questionnaire is a validated 86-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor, Inhibit, Shift, Emotional Control). For each item, parents rate whether the child engages in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 86 (better performance) and the highest is 258 (worse performance). The clinical scales form two broader Indexes (Behavioral Regulation and Metacognition) and an overall score, the Global Executive Composite (GEC). Emotion regulation was reported as the Primary Outcome. Raw scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Hyperactivity in Children When Using Vyvanse Versus Placebo by Administering the Conners-3 Parent Form

  The Conners-3 Parent Form is used to obtain the parent's observations about behavior in their child aged 6 to 18 years old. Parents rate the child's behavior on 45 items as not true at all (0) to very much true (3). The lowest scale score is 0 (better behavior) and the highest is 135 (worse behavior). The Conners 3-P includes content Scales of Inattention, Hyperactivity/Impulsivity, Learning Problems, Executive Functioning, Aggression, and Peer/Family Relations. Hyperactivity was reported as the Primary Outcome. All scores were converted to z-scores (M=0, SD=+/-1).

  12 weeks

• Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Conners-3 Parent Form

  The Conners-3 Parent Form is used to obtain the parent's observations about behavior in their child aged 6 to 18 years old. Parents rate the child's behavior on 45 items as not true at all (0) to very much true (3). The lowest scale score is 0 (better behavior) and the highest is 135 (worse behavior). The Conners 3-P includes content Scales of Inattention, Hyperactivity/Impulsivity, Learning Problems, Executive Functioning, Aggression, and Peer/Family Relations. Executive Functioning was reported as the Primary Outcome. All scores were converted to z-scores (M=0, SD=+/-1).Higher T-scores

  12 weeks

Secondary Outcomes (6)

• Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Behavior Rating Inventory of Executive Function (BRIEF) - CHILD SELF REPORT

  12 weeks

• Assessing Working Memory and Concentration in Children Using Vyvanse Versus Placebo by Measuring Performance on the Digit Span Subtest of the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V)

  12 weeks

• Assessing Sustained Attention and Response Inhibition in Children Using Vyvanse Versus Placebo by Measuring Reaction Time (RT) Standard Error (SE) on the Conners Continuous Performance Task (CPT-II).

  12 weeks

• Assessing Sustained Attention and Response Inhibition in Children Using Vyvanse Versus Placebo by Measuring RT Inter-Stimulus Interval (ISI) on the Conners Continuous Performance Task (CPT-II).

  12 weeks

• Assessing Sustained Attention and Response Inhibition in Children Using Vyvanse Versus Placebo by Measuring Hit Reaction Time (RT) Block Change on the Conners Continuous Performance Task (CPT-II).

  12 weeks

Study Arms (2)

Vyvanse

ACTIVE COMPARATOR

Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks.

Drug: Lisdexamfetamine

Placebo

PLACEBO COMPARATOR

Placebo capsule, 20-70 mg, each morning for 6 weeks.

Drug: Placebo

Interventions

Lisdexamfetamine DRUG

Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks.

Also known as: Vyvanse

Vyvanse

Placebo DRUG

Placebo capsule, 20-70 mg, each morning for 6 weeks.

Placebo

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Males and females ages 6 to 16
• Traumatic brain injury rated as mild/moderate/severe (based on Glasgow Coma Scale, estimated posttraumatic amnesia, indications of intracranial injury on CT scan, etc.)
• Sustained 2-36 months earlier
• Considered to be neurologically stable (absence of post-acute symptoms of confusion, disorientation, etc.)
• Persistent (\> 2 months) problems with focused or sustained attention
• Problems with attention/concentration rated as among the most prominent cognitive changes
• Accompanying features may include diminished arousal/speed/stamina and/or hyperactivity/impulsivity symptoms.

You may not qualify if:

• Cases with primarily penetrating head trauma
• Pre-injury history of diagnosed ADHD
• Pre-injury history of other neurodevelopmental disorders including intellectual disabilities, major communication disorders, autism spectrum disorder
• Unstable or serious psychiatric conditions, such as psychotic symptoms. Concurrent problems with depression, anxiety, or post-traumatic stress disorder may be present but are judged to be stable and not so severe as to require pharmacologic treatment
• Treatment with psychotropic medication(s), including psychostimulant(s) within the last 6 months, but eligible thereafter
• Lifetime history of stimulant abuse or dependence. Other (non-stimulant) substance abuse within the past 6 months.
• Estimated intelligence quotient (IQ) \< 70
• Sensory and/or motor impairment(s) seriously limiting testing options
• Neurological conditions including uncontrolled epilepsy, degenerative disorders, brain tumor, or stroke
• Physical condition affecting arousal, activity level, or stamina including uncontrolled thyroid dysfunction, severe or symptomatic anemia, autoimmune or metabolic disorders, untreated moderate/severe sleep apnea, etc.

Sponsors & Collaborators

• Vanderbilt University: lead
• Shire: collaborator

Study Sites (1)

Vanderbilt Medical Center

Nashville, Tennessee, 37203, 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

Results Point of Contact

• Title: Michael Tramontana,PhD
• Organization: Vanderbilt University Medical Center

michael.tramontana@vumc.org

615-327-7144

Study Officials

• Michael G Tramontana, Ph.D

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry and Neurology

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 18, 2016
• Study Start: February 6, 2017
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)