Trial Outcomes & Findings for Methylphenidate for Attention Problems After Pediatric TBI (NCT NCT01933217)
NCT ID: NCT01933217
Last Updated: 2020-06-04
Results Overview
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.
COMPLETED
PHASE4
26 participants
Reported at End of Methylphenidate Arm (Week 4 or 8)
2020-06-04
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
Placebo, Then Methlyphenidate
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.
|
|---|---|---|
|
Randomization (4 Weeks)
STARTED
|
12
|
14
|
|
Randomization (4 Weeks)
COMPLETED
|
10
|
10
|
|
Randomization (4 Weeks)
NOT COMPLETED
|
2
|
4
|
|
Crossover (4 Weeks)
STARTED
|
10
|
10
|
|
Crossover (4 Weeks)
COMPLETED
|
10
|
10
|
|
Crossover (4 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
Placebo, Then Methlyphenidate
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.
|
|---|---|---|
|
Randomization (4 Weeks)
Withdrawal by Subject
|
1
|
3
|
|
Randomization (4 Weeks)
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Methylphenidate for Attention Problems After Pediatric TBI
Baseline characteristics by cohort
| Measure |
Methylphenidate, Then Placebo
n=12 Participants
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.
|
Placebo, Then Methylphenidate
n=14 Participants
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.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
12 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=99 Participants
|
14 participants
n=107 Participants
|
26 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Reported at End of Methylphenidate Arm (Week 4 or 8)Population: All participants who completed outcome data and full cross-over intervention
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.
Outcome measures
| Measure |
Methylphenidate
n=20 Participants
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.
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.
|
Placebo
n=20 Participants
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.
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.
|
|---|---|---|
|
Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS)
Vanderbilt Parent TSS
|
1.10 units on a scale
Standard Error .11
|
1.47 units on a scale
Standard Error .11
|
|
Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS)
Vanderbilt Parent Hyperactive
|
.84 units on a scale
Standard Error .11
|
1.14 units on a scale
Standard Error .11
|
|
Parent Outcome-Vanderbilt ADHD Parent Rating Scales (VADPRS)
Vanderbilt Parent Inattentive
|
1.37 units on a scale
Standard Error .12
|
1.79 units on a scale
Standard Error .12
|
PRIMARY outcome
Timeframe: Reported at End of Methylphenidate Arm (Week 4 or 8)Population: All participants who completed outcome data and full cross-over intervention
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.
Outcome measures
| Measure |
Methylphenidate
n=20 Participants
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.
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.
|
Placebo
n=20 Participants
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.
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.
|
|---|---|---|
|
Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF)
BRIEF GEC-Overall
|
60.05 score on a scale
Standard Error 1.30
|
65.20 score on a scale
Standard Error 1.30
|
|
Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF)
BRIEF BRI-Overall
|
54.30 score on a scale
Standard Error 1.33
|
58.00 score on a scale
Standard Error 1.33
|
|
Parent Outcome-Behavior Rating Inventory of Executive Functioning (BRIEF)
BRIEF MI-Overall
|
62.40 score on a scale
Standard Error 1.52
|
67.75 score on a scale
Standard Error 1.52
|
SECONDARY outcome
Timeframe: Reported at End of Methylphenidate Arm (Week 4 or 8)Population: All participants who completed outcome data and full cross-over intervention
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.
Outcome measures
| Measure |
Methylphenidate
n=20 Participants
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.
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.
|
Placebo
n=20 Participants
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.
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.
|
|---|---|---|
|
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
|
91.25 score on a scale
Standard Error 2.24
|
SECONDARY outcome
Timeframe: January 1, 2014 - July 20, 2017Population: Challenges with engaging teachers made it difficult to collect teacher outcome measures.
Used to assess child behavior.
Outcome measures
Outcome data not reported
Adverse Events
Methylphenidate
Placebo
Serious adverse events
| Measure |
Methylphenidate
n=20 participants at risk
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.
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.
|
Placebo
n=20 participants at risk
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.
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.
|
|---|---|---|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/20 • Weeks 1-8
|
5.0%
1/20 • Number of events 1 • Weeks 1-8
|
Other adverse events
Adverse event data not reported
Additional Information
Brad Kurowski, MD, MS
Children's Hospital Medical Center, Cincinnati
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place