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

NCT ID: NCT01238822

Last Updated: 2012-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2009-06-30

Brief Summary

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.

Conditions

Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo

Low Dose Methylphenidate

Low dose: 18 mg methylphenidate

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

18 mg methylphenidate

Medium Dose Methylphenidate

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

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

36 mg methylphenidate

High Dose Methylphenidate

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

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

54 mg methylphenidate

Interventions

Methylphenidate

18 mg methylphenidate

Intervention Type: DRUG

placebo

Placebo

Intervention Type: DRUG

Methylphenidate

36 mg methylphenidate

Intervention Type: DRUG

Methylphenidate

54 mg methylphenidate

Intervention Type: DRUG

Other Intervention Names

Concerta; Concerta; Concerta

Eligibility Criteria

Inclusion 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

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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cincinnati Childrens Hospital

Cincinnati, Ohio, United States

Countries

United States

References

Froehlich TE, Epstein JN, Nick TG, Melguizo Castro MS, Stein MA, Brinkman WB, Graham AJ, Langberg JM, Kahn RS. Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2011 Nov;50(11):1129-1139.e2. doi: 10.1016/j.jaac.2011.08.002. Epub 2011 Sep 15.

Reference Type: DERIVED

PMID: 22024001 (View on PubMed)

Other Identifiers

R01MH074770

Identifier Type: NIH

Identifier Source: org_study_id

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