ADHD, TBI, Traumatic Brain Injury
Conditions
Keywords
TBI, traumatic brain injury, ADHD, methylphenidate, Concerta, attention problems
Brief summary
Traumatic Brain Injury (TBI) - methylphenidate treatment
Detailed description
The objectives of the study are to (1) determine the efficacy and dose-response of methylphenidate treatment of attention problems after pediatric traumatic brain injury (TBI) and (2) provide a better understanding of the relationship of a prior history of attention deficit hyperactivity disorder (ADHD), ADHD subtypes after TBI, executive function, and attentional control to treatment efficacy. The proposed clinical trial will enroll 50 children, age 6-17 years, with attention problems \>6 months after moderate to severe TBI into a randomized, double-blind, placebo-controlled, cross-over design trial with 3 dose conditions (low, medium, and high).
Interventions
DRUGMethylphenidate
DRUGPlacebo
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Between ages of 6-17 * Sustained Moderate to Severe TBI * TBI occurred at least 6 months prior to beginning the study * TBI occurred no earlier than 5 years of age * Positive endorsement of 6 out of 9 items on the Vanderbilt ADHD inattention or hyperactivity scale
Exclusion criteria
* History of developmental disability or mental retardation * Current active participation in ADHD-related behavioral intervention * History of psychiatric condition requiring an inpatient admission in past 12 months * Actively taking medications with a contraindication to Concerta that cannot be discontinued * Current use of stimulant medication or ADHD specific medications that cannot be discontinued * Non-blunt head injury * Family history of arrhythmia * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Reported at End of Methylphenidate Arm (Week 4 or 8) | Changes in symptom ratings were assessed on the Vanderbilt ADHD parent rating scales (VADPRS). A measure of ADHD symptom severity (Total Symptom Score \[TSS\]) is computed by totaling the scores from items 1-18 (Inattentive +Hyperactive-impulse domains), with a rating of none=0, occasionally=1, often=2, very often=3, provided. Scores for inattentive and hyperactive-impulsive domains were generated by totaling the 9 symptoms in these domains, and a TSS was computed by totaling items across domains. |
| Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | Reported at End of Methylphenidate Arm (Week 4 or 8) | The Behavior Rating Inventory of Executive Functioning (BRIEF)-Parent was used to assess executive functioning behaviors. The global executive composite (GEC), behavior regulatory index (BRI), and metacognitive index (MI) T-scores were used, with higher scores reflecting poorer executive functioning. T-scores were normalized to 50 with a standard deviation of 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuropsychological Outcome- Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI) | Reported at End of Methylphenidate Arm (Week 4 or 8) | The Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI) has been designed for children 6-16:11 years of age and provides a measure of processing speed. For this index scale, the average score is 100 with a standard deviation of 15. Higher scores reflect better processing speed. One participant was administered the Wechsler Adult Intelligence Scale 4th Edition Processing Speed Index (WAIS-IV-PSI). All scores were included in the combined WISC/WAIS processing speed variable since both measures yield highly correlated standard scores. |
| Teacher Outcome Measure | January 1, 2014 - July 20, 2017 | Used to assess child behavior. |
Countries
United States
Participant flow
Recruitment details
Recruitment period for the study was January 2014 through July 2017. Participants were recruited from a tertiary pediatric hospital in the Midwestern United States with a Level 1 trauma designation. 321 participants were screened for eligibility.
Pre-assignment details
Of the 321 assessed for eligibility, 40 participants scheduled a baseline assessment. 163 did not meet inclusion criteria and 118 declined to participate. 26 of the 40 participants were enrolled and randomized. Of those not randomized, 5 dropped before baseline visit and 9 did not show for scheduled baseline visit.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate, Then Placebo For the first week, participants received the low-dose Methylphenidate condition (Concerta® over-encapsulated). Over the subsequent 3 weeks, the dose was titrated based on medication response and side effects to determine the optimal dose used for week 4. At the end of week 4, participants crossed-over and repeated the same procedures for the placebo condition. No wash-out period was used.
The weekly dosages were low, medium, and high based on weight cut-offs. Participants weighing less than 25kg will receive 18mg (low), 27mg (medium), and 36mg (high) dosages and participants weighing above 25kg will receive 18mg (low), 36mg (medium), and 54mg (high) dosages during the 3-week upward titration trial. | 12 |
| Placebo, Then Methylphenidate For the first week, participants received the low-dose Placebo condition (white powder pills). Over the subsequent 3 weeks, the dose was titrated based on medication response and side effects to determine the optimal dose used for week 4. At the end of week 4, participants crossed-over and repeated the same procedures for the Methlyphenidate condition. No wash-out period was used.
The weekly dosages were low, medium, and high based on weight cut-offs. Participants weighing less than 25kg will receive 18mg (low), 27mg (medium), and 36mg (high) dosages and participants weighing above 25kg will receive 18mg (low), 36mg (medium), and 54mg (high) dosages during the 3-week upward titration trial. | 14 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization (4 Weeks) | Lost to Follow-up | 1 | 1 |
| Randomization (4 Weeks) | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Methylphenidate, Then Placebo | Placebo, Then Methylphenidate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 1 / 20 |
Outcome results
Primary
Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF)
The Behavior Rating Inventory of Executive Functioning (BRIEF)-Parent was used to assess executive functioning behaviors. The global executive composite (GEC), behavior regulatory index (BRI), and metacognitive index (MI) T-scores were used, with higher scores reflecting poorer executive functioning. T-scores were normalized to 50 with a standard deviation of 10.
Time frame: Reported at End of Methylphenidate Arm (Week 4 or 8)
Population: All participants who completed outcome data and full cross-over intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF GEC-Overall | 60.05 score on a scale | Standard Error 1.3 |
| Methylphenidate | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF BRI-Overall | 54.30 score on a scale | Standard Error 1.33 |
| Methylphenidate | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF MI-Overall | 62.40 score on a scale | Standard Error 1.52 |
| Placebo | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF GEC-Overall | 65.20 score on a scale | Standard Error 1.3 |
| Placebo | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF BRI-Overall | 58.00 score on a scale | Standard Error 1.33 |
| Placebo | Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF) | BRIEF MI-Overall | 67.75 score on a scale | Standard Error 1.52 |
Primary
Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS)
Changes in symptom ratings were assessed on the Vanderbilt ADHD parent rating scales (VADPRS). A measure of ADHD symptom severity (Total Symptom Score \[TSS\]) is computed by totaling the scores from items 1-18 (Inattentive +Hyperactive-impulse domains), with a rating of none=0, occasionally=1, often=2, very often=3, provided. Scores for inattentive and hyperactive-impulsive domains were generated by totaling the 9 symptoms in these domains, and a TSS was computed by totaling items across domains.
Time frame: Reported at End of Methylphenidate Arm (Week 4 or 8)
Population: All participants who completed outcome data and full cross-over intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent TSS | 1.10 units on a scale | Standard Error 0.11 |
| Methylphenidate | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent Hyperactive | .84 units on a scale | Standard Error 0.11 |
| Methylphenidate | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent Inattentive | 1.37 units on a scale | Standard Error 0.12 |
| Placebo | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent TSS | 1.47 units on a scale | Standard Error 0.11 |
| Placebo | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent Hyperactive | 1.14 units on a scale | Standard Error 0.11 |
| Placebo | Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS) | Vanderbilt Parent Inattentive | 1.79 units on a scale | Standard Error 0.12 |
Secondary
Neuropsychological Outcome- Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI)
The Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI) has been designed for children 6-16:11 years of age and provides a measure of processing speed. For this index scale, the average score is 100 with a standard deviation of 15. Higher scores reflect better processing speed. One participant was administered the Wechsler Adult Intelligence Scale 4th Edition Processing Speed Index (WAIS-IV-PSI). All scores were included in the combined WISC/WAIS processing speed variable since both measures yield highly correlated standard scores.
Time frame: Reported at End of Methylphenidate Arm (Week 4 or 8)
Population: All participants who completed outcome data and full cross-over intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Neuropsychological Outcome- Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI) | 96.05 score on a scale | Standard Error 2.24 |
| Placebo | Neuropsychological Outcome- Wechsler Intelligence Scale for Children, 4th Edition Processing Speed Index (WISC-IV-PSI) | 91.25 score on a scale | Standard Error 2.24 |
Secondary
Teacher Outcome Measure
Used to assess child behavior.
Time frame: January 1, 2014 - July 20, 2017
Population: Challenges with engaging teachers made it difficult to collect teacher outcome measures.