Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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Attention deficit with hyperactivity disorder (ADHD) is a very common behavioral problem during childhood. It is estimated that up to 80% of this disorder could be related to genetic factors. The most common treatment for ADHD is psychostimulants. In this study, the researchers investigate the effect of genetic variants in increasing the risk for behaviours pertinent to ADHD or in modulating the response of these behaviours to methylphenidate. Response to methylphenidate is evaluated through a double blind placebo controlled one week study.

Detailed Description
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Attention Deficit Hyperactivity disorder (ADHD) is a syndrome that is characterized by inattention, motor hyperactivity and impulsivity. It affects 8 to 12% of the population. The presentation of children with ADHD can be varied, from simple inattention to severe motor hyperactivity and impulsivity. It has a negative impact on the child's life, including poor school achievement and difficulty with peer and family relationships. Although the etiology of ADHD is not well understood, genetic factors are known to play a significant role in the pathogenesis of ADHD, as indicated by family, twin and adoption studies. In addition, environmental factors such as smoking during pregnancy and obstetrical complications have been found to contribute significantly in increasing the risk for and severity of ADHD. It is therefore likely that genetic predisposing factors interact with environmental factors to produce the behavioral disturbances observed in ADHD. The first goal of this study is therefore to investigate possible genetic and environmental risk factors, and examine how they might interact to confer increased risk for ADHD. A majority of children (70%) with ADHD show a significant improvement with of their behavioral disorder when treated with stimulant drugs such as methylphenidate (MPH). However, the extent to which each child benefits from MPH is variable and some of the children do not improve at all in spite of adequate trials with stimulant drugs. The second purpose of this project is to study the correlates/predictors of responsiveness to MPH in school-aged children and to identify genetic factors that may modulate the behavioral response to this drug. In order to achieve our research goals, children with ADHD are invited to participate to a two-week double-blind placebo controlled medication trial with MPH (Ritalin, 0.5mg/kg/day). During these two weeks, neuropsychological and behavioral assessments of the child are performed at the clinic to evaluate the cognitive performance of the child while on medication and placebo. Parents are invited to answer questionnaires about the behavior of their child and about family history of mental disorders, as well as prenatal and perinatal risk factors. Finally, the participating child, both parents, and siblings are invited to provide a blood or saliva sample for genetic analysis.

Official Title
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Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Ritalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ADHD Exclusion Criteria: Psychosis Tourette syndrome Intelligence quotient (IQ) < 70 Pervasive developmental disorder (PDD)

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ritalin<br> | Drug: Ritalin<br>* 0.25 mg/kg bid, orally for 7 consecutive days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* taken orally twice a day for 7 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conners' Global Index - Parent Version (CGI-P) | 10-item standardized scale evaluating ADHD symptoms; filled by parents. | Once weekly during the medication trial | 
| Conner's Global Index - Teacher Version (CGI-T) | 10-item standardized scale evaluating ADHD symptoms; filled by teachers. | Once weekly during the medication trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention Deficit Hyperactivity Disorder, Genetics, Pharmacogenetics