Methylphenidate for Attention Problems After Pediatric TBI

Efficacy of Methylphenidate for Management of Long-Term Attention Problems After Pediatric Traumatic Brain Injury (TBI)

Traumatic Brain Injury (TBI) - methylphenidate treatment

Study Overview

• Status: Completed
• Conditions: ADHD; Traumatic Brain Injury; TBI
• Intervention / Treatment: Drug: Placebo; Drug: Methylphenidate

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).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylphenidate; The study medication will consist of identical capsules filled Concerta® over-encapsulated to preserve double-blinding. The weekly dosages will be 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. Weekly ratings monitoring behavioral and side effect symptoms score and the Pittsburgh Side Effects Rating Scale.	Drug: Methylphenidate; Other Names: Concerta
Placebo Comparator: Placebo; The study medication will consist of identical capsules filled with an inert white power (placebo). Weekly ratings monitoring behavioral and side effect symptoms score and the Pittsburgh Side Effects Rating Scale.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Reported at End of Methylphenidate Arm (Week 4 or 8)
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.	Reported at End of Methylphenidate Arm (Week 4 or 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Reported at End of Methylphenidate Arm (Week 4 or 8)
Teacher Outcome Measure	Used to assess child behavior.	January 1, 2014 - July 20, 2017

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Brad Kurowski, MS, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Kurowski BG, Epstein JN, Pruitt DW, Horn PS, Altaye M, Wade SL. Benefits of Methylphenidate for Long-Term Attention Problems After Traumatic Brain Injury in Childhood: A Randomized, Double-Masked, Placebo-Controlled, Dose-Titration, Crossover Trial. J Head Trauma Rehabil. 2019 Mar/Apr;34(2):E1-E12. doi: 10.1097/HTR.0000000000000432.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 15, 2013
• First Submitted That Met QC Criteria: August 28, 2013
• First Posted (Estimate): September 2, 2013

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: ADHD; Concerta; TBI; traumatic brain injury; methylphenidate; attention problems
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: 1K23HD074683-01A1 (U.S. NIH Grant/Contract)