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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Low Dose Methylphenidate | Active Comparator | Low dose: 18 mg methylphenidate |
|
| Medium Dose Methylphenidate | Active Comparator | Medium Dosage: 36 mg if more than 50 kg and 27 mg if less than 50 kg |
|
| High Dose Methylphenidate | Active Comparator | 54 mg if more than 50 kg and 36 mg if less than 50 kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate | Drug | 18 mg methylphenidate |
|
| Measure | Description | Time Frame |
|---|---|---|
| Attention Deficit / Hyperactivity Disorder Total Sum Score of All 18 ADHD Symptom Items | Parent and teacher Vanderbilt ADHD Rating Scales - Attention Deficit / Hyperactivity Disorder Total sum score of all 18 ADHD symptom items - range equals 0-54 O - No ADHD symptoms 54 - Highest ADHD symptoms | end of first week, end of second week, end of third week, end of fourth week. Total of 4 weeks. |
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Inclusion Criteria. Participants for the study must meet all of the following criteria:
Exclusion Criteria. Potential participants will be excluded if they meet any of the following criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Childrens Hospital | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22024001 | Derived | 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. |
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Children were recruited through multiple community and clinical sources including schools and local practitioners to participate in a study of the effects of medication on cognitive functioning. Diagnostic status was determined using methodology similar to that employed by the Multimodal Treatment Study of ADHD (MTA Cooperative Group, 1999).
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All participants received 3 weekly doses of methylphenidate at a low dose (18 mg), medium dosage (27 mg or 36 mg depending on weight) and a high dosage (52 mg or 36 mg depending on weight) and another week of placebo. Patients took each dosage for 1 week and parents and teachers rated their behavior at the end of each week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants received 3 weekly doses of methylphenidate at a low dose (18 mg), medium dosage (27 mg or 36 mg depending on weight) and a high dosage (52 mg or 36 mg depending on weight) and another week of placebo. Patients took each dosage for 1 week and parents and teachers rated their behavior at the end of each week. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Attention Deficit / Hyperactivity Disorder Total Sum Score of All 18 ADHD Symptom Items | Parent and teacher Vanderbilt ADHD Rating Scales - Attention Deficit / Hyperactivity Disorder Total sum score of all 18 ADHD symptom items - range equals 0-54 O - No ADHD symptoms 54 - Highest ADHD symptoms | Intent to treat with imputation for missing data. | Posted | Mean | Standard Deviation | Score | end of first week, end of second week, end of third week, end of fourth week. Total of 4 weeks. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hallucination | Psychiatric disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Parent reported tics | Psychiatric disorders | Systematic Assessment | Number rated 4 (severe) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeff Epstein | Cincinnati Children's Hospital Medical Center | jeff.epstein@cchmc.org |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| placebo | Drug | Placebo |
|
| Methylphenidate | Drug | 36 mg methylphenidate |
|
|
| Methylphenidate | Drug | 54 mg methylphenidate |
|
|
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 |
| Medium Dosage |
36 mg methylphenidate if >25 kg; 27 mg methylphenidate if < 25 kg. |
| OG003 | High Dosage | 54 mg methylphenidate if >25 kg; 36 mg methylphenidate if < 25 kg. |
|
|
| 0 |
| 96 |
| 13 |
| 96 |
| EG001 | Low Dosage | Low dose: 18 mg methylphenidate | 0 | 96 | 12 | 96 |
| EG002 | Medium Dosage | Medium Dosage: 36 mg methylphenidate | 1 | 96 | 16 | 96 |
| EG003 | High Dosage | 54 mg methylphenidate | 0 | 96 | 37 | 96 |
|
| Parent-reported buccal-lingual movements | Nervous system disorders | Number rated 4 (severe) |
|
| Parent-reported picking at skin or fingers, nail-biting, or cheek chewing | Nervous system disorders | Number rated 4 (severe) |
|
| Parent-reported worried/anxious | Psychiatric disorders | Number rated 4 (severe) |
|
| Parent-reported dull, tired, listless | Nervous system disorders | Number rated 4 (severe) |
|
| Parent-reported headaches | Nervous system disorders | Number rated 4 (severe) |
|
| Parent-reported stomachache | Nervous system disorders | Number rated 4 (severe) |
|
| Parent-reported crabby, irritable | General disorders | Number rated 4 (severe) |
|
| Parent-reported tearful, sad, depressed | Psychiatric disorders | Number rated 4 (severe) |
|
| Parent-reported socially withdrawn | Psychiatric disorders | Number rated 4 (severe) |
|
| Parent-reported hallucinations | Psychiatric disorders | Number rated 4 (severe) |
|
| Parent-reported loss of appetite | Metabolism and nutrition disorders | Number rated 4 (severe) |
|
| Parent-reported trouble sleeping | Psychiatric disorders | Number rated 4 (severe) |
|
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| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |