Pharmacogenetic Studies on Attention Deficit Hyperactivity Disorder

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00916786
First received: June 8, 2009
Last updated: July 8, 2012
Last verified: April 2012
  Purpose

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.


Condition
Attention Deficit Hyperactivity Disorder

Study Type: Observational
Study Design: Observational Model: Case Control
Official Title: Pharmacogenetic Studies on Attention Deficit Hyperactivity Disorder

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Biospecimen Retention:   Samples With DNA

The subjects will receive blood withdrawal. The blood sample will be used for establishing lymphoblastoid cell lines, which will be used for molecular genetic experiments.


Estimated Enrollment: 240
Study Start Date: August 2009
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00916786

Contacts
Contact: Chi-Yung Shang, MD +886-2-23123456 ext 66965 cyshang@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Contact: Chi-Yung Shang, MD    +886-2-23123456 ext 66965    cyshang@ntu.edu.tw   
Principal Investigator: Chi-Yung Shang, MD         
Sub-Investigator: Susan Shur-Fen Gau, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Chi-Yung Shang, MD Dept of Psychiatry, National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00916786     History of Changes
Other Study ID Numbers: 200812153M
Study First Received: June 8, 2009
Last Updated: July 8, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Attention-deficit/hyperactivity disorder
pharmacogenetics
molecular genetics
medication response

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Methylphenidate
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014