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

NCT ID: NCT00483106

Last Updated: 2021-03-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

885 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-11-30

Study Completion Date

2020-03-31

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.

Conditions

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Attention Deficit Hyperactivity Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ritalin

Group Type ACTIVE_COMPARATOR

Ritalin

Intervention Type DRUG

0.25 mg/kg bid, orally for 7 consecutive days

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

taken orally twice a day for 7 consecutive days

Interventions

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Ritalin

0.25 mg/kg bid, orally for 7 consecutive days

Intervention Type DRUG

Placebo

taken orally twice a day for 7 consecutive days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* ADHD

Exclusion Criteria

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

6 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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McGill University

OTHER

Sponsor Role lead

Responsible Party

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Ridha Joober

Md, PhD.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ridha Joober, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Douglas Mental Health University Institute

Natalie Grizenko, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Douglas Mental Health University Institute

Locations

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Douglas Mental Health University Institute

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type DERIVED
PMID: 33453563 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29182037 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28664541 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24246434 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23185385 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23109089 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20569447 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20482957 (View on PubMed)

Other Identifiers

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99-22

Identifier Type: -

Identifier Source: org_study_id

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