Clinical trial NCT00483106: Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
Official title: Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: Attention Deficit Hyperactivity Disorder
Genetics
Pharmacogenetics
Lead sponsor: McGill University
Sponsor class: OTHER
First posted: 2007-06-06
Enrollment: 885
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* ADHD

Exclusion Criteria:

* Psychosis
* Tourette syndrome
* Intelligence quotient (IQ) \< 70
* Pervasive developmental disorder (PDD)

Primary outcomes:
measure: Conners' Global Index - Parent Version (CGI-P)
timeFrame: Once weekly during the medication trial
measure: Conner's Global Index - Teacher Version (CGI-T)
timeFrame: Once weekly during the medication trial
Secondary outcomes:
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Douglas Mental Health University Institute
state: Quebec
Study officials:
affiliation: Douglas Mental Health University Institute
name: Ridha Joober, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Douglas Mental Health University Institute
name: Natalie Grizenko, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fageera W, Chaumette B, Fortier ME, Grizenko N, Labbe A, Sengupta SM, Joober R. Association between COMT methylation and response to treatment in children with ADHD. J Psychiatr Res. 2021 Mar;135:86-93. doi: 10.1016/j.jpsychires.2021.01.008. Epub 2021 Jan 7.
citation: Naumova D, Grizenko N, Sengupta SM, Joober R. DRD4 exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate. World J Biol Psychiatry. 2019 Jul;20(6):486-495. doi: 10.1080/15622975.2017.1410221. Epub 2017 Dec 15.
citation: Fageera W, Traicu A, Sengupta SM, Fortier ME, Choudhry Z, Labbe A, Grizenko N, Joober R. Placebo response and its determinants in children with ADHD across multiple observers and settings: A randomized clinical trial. Int J Methods Psychiatr Res. 2018 Mar;27(1):e1572. doi: 10.1002/mpr.1572. Epub 2017 Jun 30.
citation: Grizenko N, Cai E, Jolicoeur C, Ter-Stepanian M, Joober R. Effects of methylphenidate on acute math performance in children with attention-deficit hyperactivity disorder. Can J Psychiatry. 2013 Nov;58(11):632-9. doi: 10.1177/070674371305801109.
citation: Thakur GA, Sengupta SM, Grizenko N, Choudhry Z, Joober R. Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy. PLoS One. 2012;7(11):e49616. doi: 10.1371/journal.pone.0049616. Epub 2012 Nov 20.
citation: Thakur GA, Sengupta SM, Grizenko N, Choudhry Z, Joober R. Family-based association study of ADHD and genes increasing the risk for smoking behaviours. Arch Dis Child. 2012 Dec;97(12):1027-33. doi: 10.1136/archdischild-2012-301882. Epub 2012 Oct 29.
citation: Thakur GA, Grizenko N, Sengupta SM, Schmitz N, Joober R. The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD. BMC Psychiatry. 2010 Jun 22;10:50. doi: 10.1186/1471-244X-10-50.
citation: Ter-Stepanian M, Grizenko N, Zappitelli M, Joober R. Clinical response to methylphenidate in children diagnosed with attention-deficit hyperactivity disorder and comorbid psychiatric disorders. Can J Psychiatry. 2010 May;55(5):305-12. doi: 10.1177/070674371005500506.