Attention Deficit Hyperactivity DisorderNCT01052753
The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention Deficit Hyperactivity Disorder (ADHD)
An observational study of Attention Deficit Hyperactivity Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The ultimate goal of this study is to find specific polymorphism of candidate genes (particularly of dopaminergic and noradrenergic systems) associated with intermediate phenotypes (e.g., executive functions, IQ, and other neuropsychological function) and/or phenomenological phenotypes (subtypes, comorbidity… Read more about this study
- Who is it for?
- Ages 7 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- How many people
- 300 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2010to 31 Jul 2013
- Phase
- Observational
- 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 7 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: The proband sample will consist of at least 150 drug-naïve children and adolescents with ADHD, aged 7-18 (who are able to perform the CANTAB and time tasks) from Department of Psychiatry, National Taiwan University Hospital (NTUH). Their biological parents (n = 300) and siblings (estimated number = 150) born to the same biological parents will be recruited as the parent controls and sibling controls, respectively, for the family-based case control study. We will recruit 150 school controls without lifetime diagnosis of ADHD in the same school districts and with similar age and gender distributions of the probands with ADHD.
Who may be able to join
- The inclusion criteria for the proband subjects are (1) that subjects have a clinical diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, which was made by a full-time board-certificated child psychiatrist at the first visit and following visits; (2) their ages range from 7 to 18 when we conduct the study; (3) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects have both biological parents; (6) both parents are Han Chinese; and (7) subjects and their biological parents (and siblings if any) consent to participate in this study for complete phenotype assessments and blood data collection.
- The inclusion criteria for the control subjects are (1) that subjects who do not have the diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, in the past and current assessments; (2) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects are Han Chinese; and (6) subjects and their mothers consent to participate in this study for complete phenotype assessments.
Who cannot join
- The proband subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with blood withdrawal or neuropsychological assessments.
- The control subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with neuropsychological assessments.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention-deficit Hyperactivity Disorder
The ultimate goal of this study is to find specific polymorphism of candidate genes (particularly of dopaminergic and noradrenergic systems) associated with intermediate phenotypes (e.g., executive functions, IQ, and other neuropsychological function) and/or phenomenological phenotypes (subtypes, comorbidity, dimensional approach) of ADHD. We propose to replicate the analysis of the candidate genes identified by previous genetic studies and recent findings from GWAS on ADHD using the candidate gene association study design (family-based case control study using parental controls and population-based case-control study). These results may lead our research team: (1) to resolve controversies over inconsistent findings in previous genetic studies and contribute to the literature on the validity of ADHD and its subtypes using clinical and genetic data; (2) to identify potential endophenotypes for ADHD genetic studies; and (3) to identify specific polymorphism of candidate genes and gene expressions of dopaminergic and noradrenergic systems associated with executive functions measured by the CANTAB.
Read the detailed description
Attention deficit hyperactivity disorder (ADHD) is a common, impairing, highly heritable, clinically heterogeneous early-onset neuropsychiatric disorder. Despite substantial evidence supporting genetic etiology of ADHD, molecular genetic studies so far have not yet provided any conclusive results using the categorical or subgroup approach of phenotype. Hence, there has been growing interest in using endophenotypes in molecular genetic studies on ADHD. Our previous studies have demonstrated significant deficits in executive functions among children with ADHD and the efficacy of methylphenidate and atomoxetine, involving dopaminergic and noradrenergic systems, in reducing ADHD core symptoms and improving executive functions. In a longitudinal follow-up family study on ADHD, we also reported that executive dysfunctions measured by the Cambridge Neuropsychological Test Automated Batteries (CANTAB) are potential endophenotypes for ADHD. Hence, identifying specific polymorphism of candidate genes of dopaminergic and noradrenergic systems associated with executive dysfunctions in Han Chinese in Taiwan is warranted.
Specific Aims:
- To identify specific genetic polymorphism of candidate genes of dopaminergic and noradrenergic systems (e.g., DRD2, DRD4, DRD5, DAT1, NET, ADRA2A, DBH, COMT etc.) associated with executive dysfunctions measured by the CANTAB and other alternative phenotype approaches (ADHD subtypes, comorbidities, treatment effects, IQ, symptom dimensions and severity);
- to investigate the relationship between a variety of ADHD phenotypes and endophenotypes and gene expressions of DRD2, DAT1, NET, ADRA2A, DBH, and COMT;
- to validate executive functions and to search for other neuropsychological functioning as endophenotypes for ADHD; and
- to determine whether ADHD is familial and identify which core symptoms of ADHD and which component of neuropsychological functioning are most familial;
Subjects and Methods: The major study design is the family-based case-control candidate gene association study. We will recruit 150 probands with ADHD, aged 7-18, and their parents (n = 300) and siblings (n= 150) and 150 school controls in three years (50, 60, and 40 families with ADHD and 50, 60, 40 school controls in the 1st, 2nd, and 3rd year, respectively). The measures include (1) interviews for psychopathology (K-SADS-E) and social functioning (SAICA), (2) self-administered questionnaires to measures ADHD symptoms (CPRS-R:S, CTRS-R:S, SNAP-IV and Adult ADHD rating scale) and comorbid conditions (ASRI and CBCL), and (3) neuropsychological tests: WISC-III-R, CPT, CANTAB, and Time Perception Tasks. The transmission/disequilibrium test (TDT) and quantitative TDT by using FBAT and FBAT-GEE, GEE, and Mixed Models will be used for data analysis.
Anticipated Results: We anticipate the establishment of clinical, neuropsychological, and genetic database of at least 350 families (150 families in this project) and 150 same-age controls, the completion of genetic analysis and gene expressions of several candidate genes including those involving dopaminergic and noradrenergic systems, and identification of genetic variants for ADHD diagnosis, symptoms, and comorbidities, executive functions, and other neurocognitive endophenotypes in a Taiwanese sample. The findings of different approaches to identify the genetic etiologies for ADHD in this study should help us determine the most promising approach for future molecular genetic studies on ADHD.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Attention-deficit/hyperactivity disorder, executive function, endophenotype, dopaminergic system, noradrenergic system, candidate gene, Family-based association study
- 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.
| Study group | Role | What they receive |
|---|---|---|
| ADHD group | Not described | |
| Control group | Not described |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study start1 Aug 2010
- Primary completion31 Jul 2013
- Study completion31 Jul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Responsible party
- Sponsor
- Investigators
- Susan Shur-Fen Gau, MD, PhD, Principal investigator, National Taiwan University Hospital & College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01052753
- Sponsor's protocol ID
- 200912118R
- Status last verified
- Sep 2021
- First submitted
- 18 Jan 2010
- Last updated
- 5 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention-deficit Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT01052753
- Acronym / sponsor ID
- 200912118R
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Attention-deficit/hyperactivity disorder, executive function, endophenotype, dopaminergic system, noradrenergic system, candidate gene, Family-based association study
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Study start
- 1 Aug 2010 (actual)
- Primary completion
- 31 Jul 2013 (actual)
- Study completion
- 31 Jul 2013 (actual)
- First posted
- 20 Jan 2010 (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.
The ultimate goal of this study is to find specific polymorphism of candidate genes (particularly of dopaminergic and noradrenergic systems) associated with intermediate phenotypes (e.g., executive functions, IQ, and other neuropsychological function) and/or phenomenological phenotypes (subtypes, comorbidity, dimensional approach) of ADHD. We propose to replicate the analysis of the candidate genes identified by previous genetic studies and recent findings from GWAS on ADHD using the candidate gene association study design (family-based case control study using parental controls and population-based case-control study). These results may lead our research team: (1) to resolve controversies over inconsistent findings in previous genetic studies and contribute to the literature on the validity of ADHD and its subtypes using clinical and genetic data; (2) to identify potential endophenotypes for ADHD genetic studies; and (3) to identify specific polymorphism of candidate genes and gene expressions of dopaminergic and noradrenergic systems associated with executive functions measured by the CANTAB.
Detailed description
Attention deficit hyperactivity disorder (ADHD) is a common, impairing, highly heritable, clinically heterogeneous early-onset neuropsychiatric disorder. Despite substantial evidence supporting genetic etiology of ADHD, molecular genetic studies so far have not yet provided any conclusive results using the categorical or subgroup approach of phenotype. Hence, there has been growing interest in using endophenotypes in molecular genetic studies on ADHD. Our previous studies have demonstrated significant deficits in executive functions among children with ADHD and the efficacy of methylphenidate and atomoxetine, involving dopaminergic and noradrenergic systems, in reducing ADHD core symptoms and improving executive functions. In a longitudinal follow-up family study on ADHD, we also reported that executive dysfunctions measured by the Cambridge Neuropsychological Test Automated Batteries (CANTAB) are potential endophenotypes for ADHD. Hence, identifying specific polymorphism of candidate genes of dopaminergic and noradrenergic systems associated with executive dysfunctions in Han Chinese in Taiwan is warranted.
Specific Aims:
- To identify specific genetic polymorphism of candidate genes of dopaminergic and noradrenergic systems (e.g., DRD2, DRD4, DRD5, DAT1, NET, ADRA2A, DBH, COMT etc.) associated with executive dysfunctions measured by the CANTAB and other alternative phenotype approaches (ADHD subtypes, comorbidities, treatment effects, IQ, symptom dimensions and severity);
- to investigate the relationship between a variety of ADHD phenotypes and endophenotypes and gene expressions of DRD2, DAT1, NET, ADRA2A, DBH, and COMT;
- to validate executive functions and to search for other neuropsychological functioning as endophenotypes for ADHD; and
- to determine whether ADHD is familial and identify which core symptoms of ADHD and which component of neuropsychological functioning are most familial;
Subjects and Methods: The major study design is the family-based case-control candidate gene association study. We will recruit 150 probands with ADHD, aged 7-18, and their parents (n = 300) and siblings (n= 150) and 150 school controls in three years (50, 60, and 40 families with ADHD and 50, 60, 40 school controls in the 1st, 2nd, and 3rd year, respectively). The measures include (1) interviews for psychopathology (K-SADS-E) and social functioning (SAICA), (2) self-administered questionnaires to measures ADHD symptoms (CPRS-R:S, CTRS-R:S, SNAP-IV and Adult ADHD rating scale) and comorbid conditions (ASRI and CBCL), and (3) neuropsychological tests: WISC-III-R, CPT, CANTAB, and Time Perception Tasks. The transmission/disequilibrium test (TDT) and quantitative TDT by using FBAT and FBAT-GEE, GEE, and Mixed Models will be used for data analysis.
Anticipated Results: We anticipate the establishment of clinical, neuropsychological, and genetic database of at least 350 families (150 families in this project) and 150 same-age controls, the completion of genetic analysis and gene expressions of several candidate genes including those involving dopaminergic and noradrenergic systems, and identification of genetic variants for ADHD diagnosis, symptoms, and comorbidities, executive functions, and other neurocognitive endophenotypes in a Taiwanese sample. The findings of different approaches to identify the genetic etiologies for ADHD in this study should help us determine the most promising approach for future molecular genetic studies on ADHD.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ADHD group | – | – |
| Control group | – | – |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The proband sample will consist of at least 150 drug-naïve children and adolescents with ADHD, aged 7-18 (who are able to perform the CANTAB and time tasks) from Department of Psychiatry, National Taiwan University Hospital (NTUH). Their biological parents (n = 300) and siblings (estimated number = 150) born to the same biological parents will be recruited as the parent controls and sibling controls, respectively, for the family-based case control study. We will recruit 150 school controls without lifetime diagnosis of ADHD in the same school districts and with similar age and gender distributions of the probands with ADHD.
Key inclusion criteria (2 listed)
- The inclusion criteria for the proband subjects are (1) that subjects have a clinical diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, which was made by a full-time board-certificated child psychiatrist at the first visit and following visits; (2) their ages range from 7 to 18 when we conduct the study; (3) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects have both biological parents; (6) both parents are Han Chinese; and (7) subjects and their biological parents (and siblings if any) consent to participate in this study for complete phenotype assessments and blood data collection.
- The inclusion criteria for the control subjects are (1) that subjects who do not have the diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, in the past and current assessments; (2) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects are Han Chinese; and (6) subjects and their mothers consent to participate in this study for complete phenotype assessments.
Key exclusion criteria (2 listed)
- The proband subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with blood withdrawal or neuropsychological assessments.
- The control subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with neuropsychological assessments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 5 Sep 2021.
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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.
Susan Shur-Fen Gau, MD, PhD principal investigator
National Taiwan University Hospital & College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Attention Deficit Hyperactivity Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
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 2 inclusion and 2 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 5 Sep 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 Taiwan. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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.
Where can I read the original study information?
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 5 Sep 2021.