Attention Deficit Hyperactivity DisorderPhase 4NCT00483106
Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
A Phase 4 study testing Ritalin in people with Attention Deficit Hyperactivity Disorder, run by McGill University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Ritalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 885 participants
- Where
- 1 siteCanada
- Study dates
- Nov 1999to 31 Mar 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ADHD
Who cannot join
- Psychosis
- Tourette syndrome
- Intelligence quotient (IQ) < 70
- Pervasive developmental disorder (PDD)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Douglas Mental Health University Institute
Montreal, Quebec, H4H 1R3
About this study
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.
Read the 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.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Ritalin, Placebo
- Keywords
- Attention Deficit Hyperactivity Disorder, Genetics, Pharmacogenetics
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitalinDrug
0.25 mg/kg bid, orally for 7 consecutive days
PlaceboDrug
taken orally twice a day for 7 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Ritalin | Active comparator | Not described Receives: Drug: Ritalin |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conners' Global Index - Parent Version (CGI-P)
10-item standardized scale evaluating ADHD symptoms; filled by parents.
Measured: Once weekly during the medication trial
Conner's Global Index - Teacher Version (CGI-T)
10-item standardized scale evaluating ADHD symptoms; filled by teachers.
Measured: Once weekly during the medication trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2007 (estimated)
- Study startNov 1999
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 885 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ridha Joober, McGill University
- Investigators
- Ridha Joober, MD, PhD, Principal investigator, Douglas Mental Health University InstituteNatalie Grizenko, MD, FRCPC, Principal investigator, Douglas Mental Health University Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00483106
- Sponsor's protocol ID
- 99-22
- Status last verified
- Mar 2021
- First submitted
- 4 Jun 2007
- Last updated
- 16 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 33453563Naumova 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.
PubMed 29182037Fageera 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.
PubMed 28664541Grizenko 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.
PubMed 24246434Thakur 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.
PubMed 23185385Thakur 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.
PubMed 23109089Thakur 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.
PubMed 20569447Ter-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.
PubMed 20482957
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
- ClinicalTrials.gov ID
- NCT00483106
- Acronym / sponsor ID
- 99-22
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Attention Deficit Hyperactivity Disorder, Genetics, Pharmacogenetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 885 participants (actual)
- Lead sponsor
- McGill UniversityUniversity, hospital or other
- Study start
- Nov 1999 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 6 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ritalin | Active comparator | Drug: Ritalin |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- ADHD
Key exclusion criteria (4 listed)
- Psychosis
- Tourette syndrome
- Intelligence quotient (IQ) < 70
- Pervasive developmental disorder (PDD)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ritalin0.25 mg/kg bid, orally for 7 consecutive days | Drug | Ritalin |
| Placebotaken orally twice a day for 7 consecutive days | Drug | Placebo |
Primary outcome
Conners' Global Index - Parent Version (CGI-P)
Time frame: Once weekly during the medication trial
10-item standardized scale evaluating ADHD symptoms; filled by parents.
Conner's Global Index - Teacher Version (CGI-T)
Time frame: Once weekly during the medication trial
10-item standardized scale evaluating ADHD symptoms; filled by teachers.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Derived from this study: PubMed 33453563Fageera 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.
- Derived from this study: PubMed 29182037Naumova 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.
- Derived from this study: PubMed 28664541Fageera 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.
- Derived from this study: PubMed 24246434Grizenko 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.
- Derived from this study: PubMed 23185385Thakur 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.
- Derived from this study: PubMed 23109089Thakur 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.
- Derived from this study: PubMed 20569447Thakur 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.
- Derived from this study: PubMed 20482957Ter-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ridha Joober, MD, PhD principal investigator
Douglas Mental Health University Institute
Natalie Grizenko, MD, FRCPC principal investigator
Douglas Mental Health University Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ritalin in people with Attention Deficit Hyperactivity Disorder, run by McGill University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conners' Global Index - Parent Version (CGI-P) (time frame: Once weekly during the medication trial). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00483106, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.