Response Variability in Children With Attention Deficit Hyperactivity Disorder (ADHD)

Cincinnati Children's Hospital Medical Center

Status and phase: Completed; Phase 4

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: placebo; Drug: Methylphenidate

Study type: Interventional

Funder types: Other

Identifiers

NCT01238822

R01MH074770

Details and patient eligibility

About

Children with Attention Deficit Hyperactivity Disorder (ADHD) have numerous areas of neuropsychological dysfunction including response inhibition, working memory, and attention. One neuropsychological outcome measure that consistently reveals between-group differences is response variability. However, until recently, differences in response variability have been reported as an ancillary finding or viewed as a nuisance in the analyses. The specific aims of the present study are to 1) Examine response variability in ADHD patients across neuropsychological tasks to understand the breadth of this specific deficit and to understand the relation between response variability and other neuropsychological outcome measures; 2) Assess whether response variability deficits are specific to either or both of the two most prevalent ADHD subtypes (i.e., Combined Type [CT] and Predominantly Inattentive Type [PIT]); 3) Determine whether response variability in ADHD patients is affected by either medication or a variety of environmental manipulations (e.g., reward); and 4) Understand the relationship between neuropsychological measures of response variability and naturalistic instances of variable performance. Forty-five children (aged 7-11) with ADHD-CT, 45 children with ADHD-PIT, and 45 normal controls will be recruited to examine response variability across a wide range of neuropsychological tests. Task parameters such as event rate, stimulus saliency, and the presence of operant reward will be modified on each test to determine the conditions under which response variability is manifested in children with ADHD. In addition, all children with ADHD will participate in a placebo-controlled, randomized medication trial with a psychostimulant medication to assess the effects of medication on response variability. Advanced analytic methods utilizing non-Gaussian distributions and fast Fourier Transforms of the reaction time data will be used to conduct detailed analyses of RT patterns across the ADHD and normal control groups. Further, the effects of task parametric manipulations and medication on response variability will be examined. Finally, relations between response variability on neuropsychological tests and response variability in a variety of real-world analog situations will be examined to evaluate the ecological validity of these deficits.

Enrollment: 96 patients

Sex: All

Ages: 7 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria. Participants for the study must meet all of the following criteria:

1. Consent: The family must provide signature of informed consent by parents or legal guardians.
2. Age at time of Screening: 7 years to 11 years, inclusive
3. Gender: includes male and female children.
4. ADHD Diagnostic Status: ADHD patients must meet DSM-IV criteria for ADHD, Inattentive or Combined subtype. Normal controls must not meet DSM-IV criteria for ADHD, any subtype. Section D.4 below describes in detail the diagnostic process for arriving at diagnosis.
5. Cognitive Functioning: IQ of greater than 80 as estimated by Vocabulary and Block Design subtests of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV).
6. Learning Disability: All children will be administered the abbreviated WIAT including the Spelling, Reading, and Math subtests. Children must score above 80 on all three WIAT subtests.
7. School: Children must be enrolled in a school setting from which teacher ratings can be obtained.

Exclusion Criteria. Potential participants will be excluded if they meet any of the following criteria:

1. Understanding Level. The patient and parent cannot understand or follow instructions given in the study.
2. History of Psychiatric Medications: Children who have a history of taking any medication for psychological or psychiatric problems will be excluded from participation.
3. Exclusionary Psychiatric Conditions: Children whose primary diagnosis is something other than ADHD will be excluded from participation.
4. Developmental Disabilities. As a result of scores on the IQ screening, additional assessments, or the judgment of the study clinicians, patients will be excluded if they are deemed to be significantly developmentally delayed. This includes clinically significant delays in cognitive function or the presence of other Pervasive Developmental Disorders (PDD).
5. Organic Brain Injury: Children must not have a history of head trauma, neurological disorder, or any other organic disorder that could possibly affect brain function.

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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96 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: placebo

Low Dose Methylphenidate

Active Comparator group

Description:

Low dose: 18 mg methylphenidate

Treatment:

Drug: Methylphenidate

Drug: Methylphenidate

Drug: Methylphenidate

Medium Dose Methylphenidate

Active Comparator group

Description:

Medium Dosage: 36 mg if more than 50 kg and 27 mg if less than 50 kg

Treatment:

Drug: Methylphenidate

Drug: Methylphenidate

Drug: Methylphenidate

High Dose Methylphenidate

Active Comparator group

Description:

54 mg if more than 50 kg and 36 mg if less than 50 kg

Treatment:

Drug: Methylphenidate

Drug: Methylphenidate

Drug: Methylphenidate