Trial Outcomes & Findings for Treatment of Traumatic Brain Injury (TBI)-Related Attention Deficits in Children (NCT NCT02712996)

NCT ID: NCT02712996

Last Updated: 2020-07-13

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 20 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2020-07-13

Participant Flow

Of 20 enrolled participants, 3 never began the trial due to scheduling problems or competing demands.

Participant milestones

Measure	Lisdexamfetamine (Vyvanse) Then Placebo Participants first received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks. On day 43 after treatment initiation, each subject was switched to placebo capsule, 20-70 mg, each morning for 6 weeks.	Placebo Then Vyvanse Participants first received Placebo capsule, 20-70 mg, each morning for 6 weeks. On day 43 after treatment initiation, participants received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks
First Intervention (Study Days 1-42) STARTED	8	9
First Intervention (Study Days 1-42) COMPLETED	8	9
First Intervention (Study Days 1-42) NOT COMPLETED	0	0
Second Intervention (Study Days 43-84) STARTED	8	9
Second Intervention (Study Days 43-84) COMPLETED	8	8
Second Intervention (Study Days 43-84) NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Lisdexamfetamine (Vyvanse) Then Placebo Participants first received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks. On day 43 after treatment initiation, each subject was switched to placebo capsule, 20-70 mg, each morning for 6 weeks.	Placebo Then Vyvanse Participants first received Placebo capsule, 20-70 mg, each morning for 6 weeks. On day 43 after treatment initiation, participants received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks
Second Intervention (Study Days 43-84) Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Lisdexamfetamine (Vyvanse) Then Placebo n=8 Participants Participants first received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks. Then on day 43 after treatment initiation, each subject received Placebo capsule, 20-70 mg, each morning for 6 weeks	Placebo Then Lisdexamfetamine (Vyvanse) n=9 Participants Participants first received Placebo capsule, 20-70 mg, each morning for 6 weeks. Then on day 43 after treatment initiation, each subject received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning for 6 weeks.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	9 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event.

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	1.00 Z-score Standard Deviation 1.11	1.76 Z-score Standard Deviation 1.47

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Behavior Rating Inventory of Executive Function (BRIEF) - PARENT	0.51 Z-score Standard Deviation 0.99	1.16 Z-score Standard Deviation 1.33

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Inattentiveness in Children Using Vyvanse Versus Placebo by Measuring Omissions on the Conners Continuous Performance Task (CPT-II).	0.63 Z score Standard Deviation 1.71	1.33 Z score Standard Deviation 1.68

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Physical Symptoms in Children Using Vyvanse Versus Placebo by Measuring Anxiety on the Revised Child Manifest Anxiety Scale (RCMAS)	0.12 Z-score Standard Deviation 0.79	-0.23 Z-score Standard Deviation 0.95

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Total Symptoms in Children Using Vyvanse Versus Placebo by Measuring Anxiety on the Revised Child Manifest Anxiety Scale (RCMAS)	-0.3 Z-score Standard Deviation 0.85	-0.56 Z-score Standard Deviation 0.89

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Attention Problems in Children Using Vyvanse Versus Placebo by Measuring Symptoms on the Child Behavior Checklist (CBCL)	0.88 Z-score Standard Deviation 0.69	1.37 Z-score Standard Deviation 0.93

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Anxiety-Depression Problems in Children Using Vyvanse Versus Placebo by Measuring Symptoms on the Child Behavior Checklist (CBCL)	0.44 Z-score Standard Deviation 0.52	0.76 Z-score Standard Deviation 0.66

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Inhibitory Control in Children When Using Vyvanse Versus Placebo Utilizing the Inhibit Subscale on the Behavior Rating Inventory of Executive Function (BRIEF) - PARENTS	-0.05 Z-score Standard Deviation 1.05	0.42 Z-score Standard Deviation 1.16

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.33 Z-score Standard Deviation 1.22	1 Z-score Standard Deviation 1.44

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.64 Z-score Standard Deviation 0.89	1.23 Z-score Standard Deviation 1.04

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.96 Z-score Standard Deviation 1.25	1.69 Z-score Standard Deviation 1.26

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.34 Z-score Standard Deviation 0.89	0.84 Z-score Standard Deviation 1.19

PRIMARY outcome

Timeframe: 12 weeks

Population: All participants who received at least one dose of each intervention were included in the efficacy analysis.

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	-0.04 Z-score Standard Deviation 1.12	0.48 Z-score Standard Deviation 1.21

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.68 Z-score Standard Deviation 1.02	1.33 Z-score Standard Deviation 1.31

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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	0.35 Z-score Standard Deviation 1.16	0.94 Z-score Standard Deviation 1.39

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Hyperactivity in Children When Using Vyvanse Versus Placebo by Administering the Conners-3 Parent Form	0.075 Z-score Standard Deviation 1.45	0.71 Z-score Standard Deviation 1.56

PRIMARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Conners-3 Parent Form	0.97 Z-score Standard Deviation 1.24	1.79 Z-score Standard Deviation 1.58

SECONDARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

The BRIEF Self-Report Version assesses an adolescent's (ages 11-18) view of his or her cognitive, emotional, and behavioral functions. It is a validated 55-item questionnaire composed of 8 clinical scales that measure different aspects of executive functioning (Inhibit, Shift, Emotional Control, Monitor, Working Memory, Plan/Organize, Organization of Materials, and Task Completion). For each item, the child rates whether they engage in the behavior "never" (=1), "sometimes" (=2), or "often" (=3). The lowest scale score is 55 (better performance) and the highest is 165 (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).

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Executive Functioning in Children When Using Vyvanse Versus Placebo by Administering the Behavior Rating Inventory of Executive Function (BRIEF) - CHILD SELF REPORT	0.66 Z-score Standard Deviation 1.08	0.59 Z-score Standard Deviation 1.14

SECONDARY outcome

Timeframe: 12 weeks

Population: 1 participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

Digit Span repeats strings of digits of increasing length said by the examiner. Participants were asked to repeat the digits in the same sequence, either forwards or backwards. Every item on Digit Span consists of two trials. One point was awarded if the participant passed only 1 trial of a sequence length. Zero points were given if the participant failed both trials. It measures working memory and concentration with a range of scaled scores from 0-19. Raw scores were converted to z-scores (M=0, SD=+/-1). Higher scores indicate better recall and attention.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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)	-0.27 Z-score Standard Deviation 0.84	-0.29 Z-score Standard Deviation 1.01

SECONDARY outcome

Timeframe: 12 weeks

Population: Missing data from 2 participants in the Placebo arm and 2 participants in the Vyvanse arm

Conner's Continuous Performance Task (CPT-II) measure 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). Raw scores were converted to z-scores (M=0, SD=+/-1). Hit Reaction Time (RT) Standard Error (SE) measures response speed consistency. The higher the Overall Standard Error, the greater the inconsistency in the response speed, indicating a greater amount of inattention.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=14 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=15 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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).	0.14 Z-score Standard Deviation 1.28	0.57 Z-score Standard Deviation 1.53

SECONDARY outcome

Timeframe: 12 weeks

Population: This assessment was not administered.

Conner's Continuous Performance Task (CPT-II) measure 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). 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks

Population: 1 participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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). Raw scores were converted to z-scores (M=0, SD=+/-1). Overall hit reaction time is the average speed of correct responses for the entire test. Lower values indicate that responses got quicker as the test progressed. High values indicate a substantial slowing in reaction times.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
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).	0.75 Z-score Standard Deviation 1.49	1.19 Z-score Standard Deviation 1.39

SECONDARY outcome

Timeframe: 12 weeks

Population: One participant completed the placebo arm, but dropped out of Vyvanse arm due to adverse event

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). CPT-II Perseverations 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. Raw scores were converted to z-scores (M=0, SD=+/-1) to have them on a uniform metric. Higher scores indicate greater inattentiveness.

Outcome measures

Measure	Lisdexamfetamine (Vyvanse) n=16 Participants Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.	Placebo n=17 Participants Participants who received Placebo capsule, 20-70 mg, each morning in either the or last 6 weeks of the study.
Assessing Sustained Attention and Response Inhibition in Children Using Vyvanse Versus Placebo by Measuring Perseverations on the Conners Continuous Performance Task (CPT-II).	1.02 Z-score Standard Deviation 1.89	0.86 Z-score Standard Deviation 1.69

Adverse Events

Lisdexamfetamine (Vyvanse)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lisdexamfetamine (Vyvanse) n=17 participants at risk Participants who received Lisdexamfetamine (Vyvanse) capsule, 20-70 mg, each morning in either the first or last 6 weeks of the study.	Placebo n=17 participants at risk Participants who received Placebo capsule, 20-70 mg, each morning in either the first or last 6 weeks of the study.
General disorders Anxiety	5.9% 1/17 • Number of events 1 • 12 weeks	0.00% 0/17 • 12 weeks

Additional Information

Michael Tramontana,PhD

Vanderbilt University Medical Center

Phone: 615-327-7144

Email: michael.tramontana@vumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place