Pharmacogenetic Studies on Attention Deficit Hyperactivity Disorder

September 1, 2021 updated by: National Taiwan University Hospital
The ultimate goal of this study is to find the association between specific polymorphism of candidate genes and medication response in attention deficit hyperactivity disorder (ADHD) patients. These results will lead the investigators' team: (1) to resolve controversies over inconsistent findings in previous pharmacogenetic studies; (2) to study the medication effect on the neuropsychological functions that are useful candidate endophenotypes for ADHD; (3) to delineate the nature and the effect of gene-gene interaction in the drug response of ADHD patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Background: The science of pharmacogenetics seeks to identify patterns of genetic variation that will direct individually tailored treatment regimens and enhance long-term adherence. Attention deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity and impulsivity, is an early onset, highly heritable, clinically heterogeneous, long-term impairing disorder with tremendous impact on individuals, families, and societies. It affects 5-10% of school-aged children worldwide (7.5% in Taiwan) and 2-4% of adults. Although the efficacy of medications for ADHD is well demonstrated in clinical trials, substantial numbers of patients fail to remain on therapy, and there is tremendous variability in tolerability and treatment acceptance. An understanding of genetic predictors of ADHD medication response is likely to influence future clinical treatments, inform research on treatment-resistant ADHD patients, and identify patients at increased risk for significant treatment related adverse events. Although interest in ADHD pharmacogenetics is encouraging, conflicting results in previous studies may reflect genetic heterogeneity and differences in phenotype, and medication response in ADHD children likely results from the combined effects of several potential genes. In addition, the categorical measure of treatment effects and retrospective study design may not have been sensitive enough to pick up statistically significant differences in treatment response based on genotype. Further prospective studies including quantitative measures of medication response are warranted.

Specific Aims:

  1. to assess the specific genetic moderators of methylphenidate and atomoxetine response using repeated outcome measurements;
  2. to examine the association between genetic polymorphisms and medication effects on the neuropsychological functions;
  3. to identify the gene-gene interactions in pharmacogenetics for ADHD. Subjects and Methods: We will recruit 160 drug-naïve ADHD patients and 80 matched normal controls, aged 7-18. The patients will be randomly assigned to two treatment groups, the OROS-methylphenidate group (n=80) and the atomoxetine group (n=80), respectively. After complete assessment at baseline and administration of either OROs-methylphenidate or atomoxetine, patients with ADHD will be reassessed at Week 2, 4, 8, 12, 16, and 24 mainly for vital signs, behavioral symptoms, and psychosocial functions evaluations using the SNAP-IV, YSR, CBCL, CGI-ADHD-S, CGI-ADHD-I, SAICA, and Family APGAR-C. Neuropsychological tests, including CPT, Time Perception Tasks, and CANTAB, will be performed at Week 4 and 16. The DNA will be collected, and the candidate genes (DAT1, DRD4, DRD5, SLC6A2, and SLC6A4) hypothesized to influence medication effects or individual risks for ADHD will be genotyped.

Anticipated Results: We anticipate that this study will delineate the pharmacogenetics for ADHD by determining the association between medication response and genetic variants in a Taiwanese sample. The findings of different approaches to identify the effects of genotypes on the drug response in this study should help us to extend our understanding of the genetic basis of ADHD. Development of individualized medication regimens based on patient genetic variability might lead to optimized symptom reduction, improved tolerability, and concomitant improvements in patient adherence. Conversely, patients with increased genetic risk for treatment failure or significant adverse effects could be spared exposure to certain compounds that are of unlikely benefit. Pharmacogenetics also has a potential role in the development of new compounds for ADHD therapy. The use of genetic screening in dosing will provide a model for future drug development, in which outcome variability is assessed in genetic subgroups and not merely on the basis of treatment assignment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
240

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

7 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The sample will consist of 160 drug-naïve ADHD patients and 80 matched normal controls, aged 7-18. The patients will be randomly assigned to two treatment groups, the OROS-methylphenidate group (n=80) and the atomoxetine group (n=80), respectively.

Description

Inclusion Criteria:

Patients are eligible to be included in this study only if they meet all of the following criteria:

  1. Patients will be outpatients who are between 7 and 18 years of age.
  2. Patients must have ADHD that meet the Diagnostic and Statistical Manual of Mental disorders, 4th edition (DSM-IV) disease diagnostic criteria assessed by the investigator's clinical evaluation, as well as confirmed by the Chinese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version (K-SADS-E).
  3. Patients must have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score > 4 at Visit 1.
  4. Patients must be psychotropic medication-naïve. Patients will be considered to be medication-naïve if they have never received medications specifically to treat ADHD.
  5. Patients must have laboratory results, including serum chemistries, hematology, and urine analysis showing no significant abnormalities and no clinical information that should preclude a patient's participation at study entry. A patient with a significant abnormal laboratory result mat enter the study if, after appropriate medical evaluation, the result dose not indicate a serious medical condition that in the investigator's judgment would preclude participation.
  6. Patients and parents (or legal representative) must have a degree of understanding sufficient to be able to communicate suitably with the investigator.
  7. Patients must be of normal intelligence in the judgment of the investigator. Normal intelligence is defined as achieving a score of 80 or more when IQ testing is administrated.
  8. Patients must have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, including neuropsychological testing and venipunctures.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

  1. Patients with current or past history of schizophrenia, schizoaffective Disorder, organic psychosis, bipolar I or II disorder, autism, Asperger's disorder, or pervasive developmental disorder. Other comorbid psychiatric disorders are not excluded if the ADHD symptoms are the primary source of impairment for the patient.
  2. Patients with a history of any seizure disorder (other than febrile convulsion) or patients who are taking anticonvulsants for seizure control.
  3. Patients have been at serious suicidal risk, determined by the investigator.
  4. Patients with a history of severe allergies to more than one class of medications or multiple adverse drug reactions.
  5. Patients with a history of alcohol or drug abuse within the past 3 months, or who are currently using alcohol, drugs of abuse, or any described or over-the-counter medication in a manner that the investigator considers indicative of abuse.
  6. Patients with cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure.
  7. Patients who are likely to need psychotropic medications apart from methylphenidate or atomoxetine, including Chinese medicine or health-food supplements that have central nervous system activity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
OROS-methylphenidate
The patients will be randomly assigned to two treatment groups, the OROS-methylphenidate group (n=80) and the atomoxetine group (n=80), respectively.
Atomoxetine group
The patients will be randomly assigned to two treatment groups, the OROS-methylphenidate group (n=80) and the atomoxetine group (n=80), respectively.
Control group
Healthy controls matching for the distribution of age and sex of the case groups

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Taiwan University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Science Council, Taiwan

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2009

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 200812153M

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