Attention-deficit/Hyperactivity DisorderPhase 4NCT02074228
Identify Peripheral Biomarkers of Symptomatology, Neurocognitive Functions, and Medication Response in ADHD
A Phase 4 study testing Methylphenidate (Concerta) in people with Attention-deficit/Hyperactivity Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 7 to 16 years
- Conditions the study is for
- Attention-deficit/Hyperactivity Disorder
- What is being tested?
- Methylphenidate (Concerta)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2012to Jul 2015
- 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 7 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients will be outpatients who are between 7 and 16 years of age.
- 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).
- Patients must have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score > 4 at Visit 1.
- Patients must be psychotropic medication-naïve. Patients will be considered to be medication-naïve if they have never received medications specifically to treat ADHD.
- 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 may enter the study if, after appropriate medical evaluation, the result does not indicate a serious medical condition that in the investigator's judgment would preclude participation.
- Patients and parents (or legal representative) must have a degree of understanding sufficient to be able to communicate suitably with the investigator.
- 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.
- 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.
Who cannot join
- 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.
- Patients with a history of any seizure disorder (other than febrile convulsion) or patients who are taking anticonvulsants for seizure control.
- Patients have been at serious suicidal risk, determined by the investigator.
- Patients with a history of severe allergies to more than one class of medications or multiple adverse drug reactions.
- 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.
- Patients with cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure.
- Patients who are likely to need psychotropic medications apart from methylphenidate, including Chinese medicine or health-food supplements that have central nervous system activity.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
college of Medicine, National Taiwan University
Taipei
Chi-Yung Shang, MA, +886-2-2312-3456 ext. 66965, cyshang@ntu.edu.tw
Shur-Fen Susan Gau, Ph. D, +886-2-2312-3456 ext. 66802, Gaushufe@ntu.edu.tw
About this study
Official title: A Study to Identify the Peripheral Biomarkers of Symptomatology, Neurocognitive Functions, and Medication Response in Attention Deficit Hyperactivity Disorder
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. It is of great interest to identify biomarkers relating to medication response in ADHD. However, the procedure for obtaining central markers such as PET scan is invasive and expensive. Previous studies have found that mRNA expression of neurochemical markers in circulating blood can reflect the neurochemical levels in the brain. Further studies to identify peripheral biomarkers related to medication response in ADHD are warranted.
Read the detailed description
Specific Aims:
- to examine the relationship between peripheral mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) and symptomatology of ADHD;
- to examine the relationship between peripheral mRNA expression levels of dopamine markers and neurocognitive endophenotypes of ADHD;
- to identify the specific dopamine markers of methylphenidate effects on the symptomatology of ADHD;
- to identify the specific dopamine markers of methylphenidate effects on the neurocognitive endophenotypes of ADHD.
Subjects and Methods: We will recruit 120 drug-naïve ADHD patients, aged 7-18 in this 3-year project. The patients will receive methylphenidate, and the medication response will be assessed regularly within 12-week treatment period (Week 0, 2, 4, 8, and 12). The primary efficacy measure is the ADHDRS and CGI-ADHD-S. The secondary measures include the SNAP-IV, CBCL, CGI-ADHD-I, SAICA, and Family APGAR. Neuropsychological testing, including WISC-III, CPT, and CANTAB, will be performed. The blood sample will be collected, and the mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) hypothesized to influence medication effects risks for ADHD will be analyzed.
Anticipated Results: Our study will identify peripheral dopamine biomarkers that can predict individual variability in symptomatology and neurocognitive functions following treatment with methylphenidate. The ability of peripheral biomarkers to predict response to methylphenidate administration can have important implications for personalizing the treatment for ADHD, allowing clinicians to predict which patients will receive greatest benefit from dopaminergic medications. The use of mRNA screening in dosing will provide a model for future drug development, in which outcome variability is assessed in subgroups of peripheral dopamine markers and not merely on the basis of treatment assignment. In addition, the findings of such approaches to identify the peripheral biomarkers on the drug response in this study should help us to extend our understanding of the pathophysiological mechanism of ADHD.
- Conditions
- Attention-deficit/Hyperactivity Disorder
- Being tested
- Methylphenidate (Concerta)
- Keywords
- Attention-deficit/hyperactivity disorder,, symptomatology,, neurocognitive endophenotype,, medication response
- 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.
Methylphenidate (Concerta)Drug
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate | Experimental | Methylphenidate (Concerta) 18mg or 36mg 1# qd, 12 weeks Receives: Drug: Methylphenidate (Concerta) |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADHD Rating Scale-IV
Evaluate the symptom change after medication
Measured: baseline and 12 weeks after treatment
Secondary outcomes (2)
SNAP-IV
Measured: Baseline and 12 weeks after treatment
Safety Questionnaire
Measured: baseline and 12 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2014 (estimated)
- Study startAug 2012
- Primary completionJul 2015 (estimated)
- Study completionJul 2015 (estimated)
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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Responsible party
- Sponsor
- Investigators
- Chi-Yung Shang, M.D., Ph.D., Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02074228
- Sponsor's protocol ID
- 201112131MIB
- Status last verified
- Feb 2014
- First submitted
- 6 Sep 2012
- Last updated
- 28 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Identify the Peripheral Biomarkers of Symptomatology, Neurocognitive Functions, and Medication Response in Attention Deficit Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT02074228
- Acronym / sponsor ID
- 201112131MIB
- Conditions
- Attention-deficit/Hyperactivity Disorder
- Keywords
- Attention-deficit/hyperactivity disorder,, symptomatology,, neurocognitive endophenotype,, medication response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Study start
- Aug 2012
- Primary completion
- Jul 2015 (estimated)
- Study completion
- Jul 2015 (estimated)
- First posted
- 28 Feb 2014 (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 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. It is of great interest to identify biomarkers relating to medication response in ADHD. However, the procedure for obtaining central markers such as PET scan is invasive and expensive. Previous studies have found that mRNA expression of neurochemical markers in circulating blood can reflect the neurochemical levels in the brain. Further studies to identify peripheral biomarkers related to medication response in ADHD are warranted.
Detailed description
Specific Aims:
- to examine the relationship between peripheral mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) and symptomatology of ADHD;
- to examine the relationship between peripheral mRNA expression levels of dopamine markers and neurocognitive endophenotypes of ADHD;
- to identify the specific dopamine markers of methylphenidate effects on the symptomatology of ADHD;
- to identify the specific dopamine markers of methylphenidate effects on the neurocognitive endophenotypes of ADHD.
Subjects and Methods: We will recruit 120 drug-naïve ADHD patients, aged 7-18 in this 3-year project. The patients will receive methylphenidate, and the medication response will be assessed regularly within 12-week treatment period (Week 0, 2, 4, 8, and 12). The primary efficacy measure is the ADHDRS and CGI-ADHD-S. The secondary measures include the SNAP-IV, CBCL, CGI-ADHD-I, SAICA, and Family APGAR. Neuropsychological testing, including WISC-III, CPT, and CANTAB, will be performed. The blood sample will be collected, and the mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) hypothesized to influence medication effects risks for ADHD will be analyzed.
Anticipated Results: Our study will identify peripheral dopamine biomarkers that can predict individual variability in symptomatology and neurocognitive functions following treatment with methylphenidate. The ability of peripheral biomarkers to predict response to methylphenidate administration can have important implications for personalizing the treatment for ADHD, allowing clinicians to predict which patients will receive greatest benefit from dopaminergic medications. The use of mRNA screening in dosing will provide a model for future drug development, in which outcome variability is assessed in subgroups of peripheral dopamine markers and not merely on the basis of treatment assignment. In addition, the findings of such approaches to identify the peripheral biomarkers on the drug response in this study should help us to extend our understanding of the pathophysiological mechanism of ADHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate | Experimental | Drug: Methylphenidate (Concerta)Methylphenidate (Concerta) 18mg or 36mg 1# qd, 12 weeks |
Who may qualify
- Ages
- 7 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Patients will be outpatients who are between 7 and 16 years of age.
- 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).
- Patients must have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score > 4 at Visit 1.
- Patients must be psychotropic medication-naïve. Patients will be considered to be medication-naïve if they have never received medications specifically to treat ADHD.
- 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 may enter the study if, after appropriate medical evaluation, the result does not indicate a serious medical condition that in the investigator's judgment would preclude participation.
Key exclusion criteria (7 listed)
- 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.
- Patients with a history of any seizure disorder (other than febrile convulsion) or patients who are taking anticonvulsants for seizure control.
- Patients have been at serious suicidal risk, determined by the investigator.
- Patients with a history of severe allergies to more than one class of medications or multiple adverse drug reactions.
- 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.
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 |
|---|---|---|
| Methylphenidate (Concerta) | Drug | Methylphenidate |
Primary outcome
ADHD Rating Scale-IV
Time frame: baseline and 12 weeks after treatment
Evaluate the symptom change after medication
2 secondary outcomes
SNAP-IV
Time frame: Baseline and 12 weeks after treatment
Safety Questionnaire
Time frame: baseline and 12 weeks after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2014.
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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.
Chi-Yung Shang, M.D., Ph.D. principal investigator
National Taiwan University Hospital
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 Methylphenidate (Concerta) in people with 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 8 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 28 Feb 2014. 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.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chi-Yung Shang, Ph.D. (+886-2-2312-3456 ext. 66965, cyshang@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADHD Rating Scale-IV (time frame: baseline and 12 weeks after treatment). It is what the study was designed to measure, not a finding.
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 28 Feb 2014.