Attention Deficit Hyperactivity DisorderNCT02642068
Neuropsychology, Neuroimage and Neurophysiology in Adults With ADHD
An observational study of Attention Deficit Hyperactivity Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
We anticipate that drug-naïve ADHD probands, particularly those with DAT1 or SLC6A2 gene variants may have higher level of altered microstructural integrity of frontostriatal (FS), frontoparietal (FP), other hypothesized fiber tracts and decreased brain activity of FS, FP, and other circuits, deficits in ERP, and… Read more about this study
- Who is it for?
- Ages 16 to 30 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- How many people
- 300 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2014to 31 Jul 2019
- 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 16 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: This 5-year proposal consists of two parts: (1) a 3-year case-control study with unaffected siblings and adult neurotypicals as controls to investigate the brain structural connectivity, functional connectivity, neurophysiological, neuropsychological functioning in 60 probands with ADHD, their unaffected siblings (at least 30 same-sex siblings, n=30~60) and age-, sex-, handedness-, and IQ-matched neurotypicals (n=90~120) with estimated total sample size as at least 180 up to 240. (2) a 2-year follow-up study to repeat the neuropsychological and MRI assessments and to assess electrophysiology related to inhibition controls of 40 adolescents and young adults with childhood diagnosis of ADHD and 40 neurotypicals who had same neuropsychological and imaging assessments in 2010.8-1013.7.
Who may be able to join
- Subjects aged 16-30, who have clinical diagnosis of a ADHD according to the DSM-IV and DSM-5 diagnostic criteria, and who have never been treated with medication for ADHD treatment. At least 30 out of 60 subjects have same-sex unaffected siblings.
Who cannot join
- The subjects will be excluded from the study if they meet any of the following criteria: (1) Comorbidity with DSM-IV-TR or DSM-5 diagnoses of autism spectrum disorder, schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, organic psychosis, schizotypal personality disorder, bipolar disorder, depression, severe anxiety disorders or substance use; (2) With neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, and history of craniotomy; (3)With visual or hearing impairments, or motor disability which may influence the process of MRI assessment; and (4) Full-scale IQ lower than 80.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuropsychology, Neuroimage and Neurophysiology in Adults With Attention-Deficit Hyperactivity Disorder: An Endophenotype and Follow-up Study
We anticipate that drug-naïve ADHD probands, particularly those with DAT1 or SLC6A2 gene variants may have higher level of altered microstructural integrity of frontostriatal (FS), frontoparietal (FP), other hypothesized fiber tracts and decreased brain activity of FS, FP, and other circuits, deficits in ERP, and impaired EF, SA, IIA and VM than probands without DAT1 or SLC6A2 gene variants or adult neurotypical. The alterations in the structural and functional connectivity, neurophysiological and neuropsychological functioning would be observed in the unaffected siblings as compared to neurotypical. The unaffected siblings will be in the intermediate position between drug-naïve adult ADHD probands and neurotypical. The genetic dosage is anticipated to pose the strongest effects on the cortical thickness, brain volume, gyrification and microstructural property of white matter, followed by neurophysiology, functional connectivity, and neuropsychological function with the least effect.
In terms of longitudinal follow-up part, we also anticipated despite increasing thinning of cortical thickness, microstructural integrity of several targets fiber tracts, and brain activity of target brain regions and improving performance in EF, SA, IIV, VM from childhood to late adolescence and young adulthood in the neurotypical group, the slopes of developmental trajectories of these neuroimaging and neuropsychological function are lower in the ADHD group.
Read the detailed description
Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Despite extensive research in adult ADHD in western countries, there has been no published data about adult ADHD in Taiwan except the PI's and colleagues' previous works on pharmacotherapy in adults with ADHD and only few endophenotype studies based on adults with ADHD in the world. The ultimate goals of this 5-year project are to identify which neuropsychological, functional and structural connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers) for ADHD based on unaffected sibling (1st-3rd years) and follow-up (4th-5th years) designs. With the accomplishment of the following study goals, this study will be the first study on the topics of neuroimaging and neurophysiological endophenotypes on adult ADHD using advanced imaging techniques (i.e., Tract-based autonomic analysis, TBAA) and comprehensive clinical and neurocognitive data. This proposal has one primary aim and four secondary aims:
Primary Aim:
- To validate structural (assessed by TBAA using diffusing spectrum imaging, DSI) and functional connectivity (assessed by resting-state fMRI) in frontostriatal, frontoparietal and other circuitries, and neurophysiological functions (assessed by stop-signal event-related potential [ERP]: N2, P3, ERN, Pe) as effective imaging endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and age-, sex-, handedness-, and IQ-matched adult neurotypical and association with DAT1 and NET (SLC6A2) variants; Secondary Aims:
- To validate the executive functions (EF), sustained attention (SA), intraindividual variability (IIV), visual-spatial memory (VM) as effective neurocognitive endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and adult neurotypical;
- To examine the developmental trajectory and stability of neuropsychological functions and structural and functional connectivity from childhood to adolescence and young adulthood;
- To correlate the data from structural (morphometric, cortical thickness, gyrification, fiber tract integrity) and functional connectivity (rsfMRI), neuropsychology (Executive function, visual-spatial memory, sustained attention, variability), neurophysiology (Stop-signal ERP) and ADHD core symptoms stratifying by the presence of ADHD, presence of DAT1 and NET (SLC6A2) variants, proband-unaffected sibling dyads, and different developmental stages.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Drug-naïve Adult ADHD, Neuropsychology, Neurophysiology, Neuroimaging, Follow-up
- 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 | Drug-naïve adult ADHD Probands | |
| Sibling group | Unaffected Siblings of Drug-naïve Adult ADHD | |
| Control group | Age-, sex-, handedness-, and IQ-matched controls without lifetime ADHD or a family history of ADHD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural neuroimaging
Using diffusing spectrum imaging (DSI) to assess the structural connectivity in frontostriatal, frontoparietal and other circuitries
Measured: 1 day
Secondary outcomes (1)
Functional connectivity of the brain circuits
Using resting-state functional MRI (rsfMRI) to assess the functional connectivity in frontostriatal, frontoparietal and other circuitries.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2015 (estimated)
- Study start1 Aug 2014
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- 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
- NCT02642068
- Sponsor's protocol ID
- 201401024RINC
- Status last verified
- Sep 2021
- First submitted
- 25 Aug 2014
- Last updated
- 2 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chang JC, Lin HY, Gau SS. Age-dependent effects of cumulative methylphenidate exposure on brain structure and symptom amelioration in youth with ADHD: A longitudinal MRI study. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111429. doi: 10.1016/j.pnpbp.2025.111429. Epub 2025 Jun 15.
PubMed 40527386Lee CY, Goh JOS, Gau SS. Differential neural processing of value during decision-making in adults with attention-deficit/hyperactivity disorder and healthy controls. J Psychiatry Neurosci. 2023 Mar 29;48(2):E115-E124. doi: 10.1503/jpn.220123. Print 2023 Mar-Apr.
PubMed 36990469
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuropsychology, Neuroimage and Neurophysiology in Adults With Attention-Deficit Hyperactivity Disorder: An Endophenotype and Follow-up Study
- ClinicalTrials.gov ID
- NCT02642068
- Acronym / sponsor ID
- 201401024RINC
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Drug-naïve Adult ADHD, Neuropsychology, Neurophysiology, Neuroimaging, Follow-up
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Aug 2014 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 30 Dec 2015 (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.
We anticipate that drug-naïve ADHD probands, particularly those with DAT1 or SLC6A2 gene variants may have higher level of altered microstructural integrity of frontostriatal (FS), frontoparietal (FP), other hypothesized fiber tracts and decreased brain activity of FS, FP, and other circuits, deficits in ERP, and impaired EF, SA, IIA and VM than probands without DAT1 or SLC6A2 gene variants or adult neurotypical. The alterations in the structural and functional connectivity, neurophysiological and neuropsychological functioning would be observed in the unaffected siblings as compared to neurotypical. The unaffected siblings will be in the intermediate position between drug-naïve adult ADHD probands and neurotypical. The genetic dosage is anticipated to pose the strongest effects on the cortical thickness, brain volume, gyrification and microstructural property of white matter, followed by neurophysiology, functional connectivity, and neuropsychological function with the least effect.
In terms of longitudinal follow-up part, we also anticipated despite increasing thinning of cortical thickness, microstructural integrity of several targets fiber tracts, and brain activity of target brain regions and improving performance in EF, SA, IIV, VM from childhood to late adolescence and young adulthood in the neurotypical group, the slopes of developmental trajectories of these neuroimaging and neuropsychological function are lower in the ADHD group.
Detailed description
Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Despite extensive research in adult ADHD in western countries, there has been no published data about adult ADHD in Taiwan except the PI's and colleagues' previous works on pharmacotherapy in adults with ADHD and only few endophenotype studies based on adults with ADHD in the world. The ultimate goals of this 5-year project are to identify which neuropsychological, functional and structural connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers) for ADHD based on unaffected sibling (1st-3rd years) and follow-up (4th-5th years) designs. With the accomplishment of the following study goals, this study will be the first study on the topics of neuroimaging and neurophysiological endophenotypes on adult ADHD using advanced imaging techniques (i.e., Tract-based autonomic analysis, TBAA) and comprehensive clinical and neurocognitive data. This proposal has one primary aim and four secondary aims:
Primary Aim:
- To validate structural (assessed by TBAA using diffusing spectrum imaging, DSI) and functional connectivity (assessed by resting-state fMRI) in frontostriatal, frontoparietal and other circuitries, and neurophysiological functions (assessed by stop-signal event-related potential [ERP]: N2, P3, ERN, Pe) as effective imaging endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and age-, sex-, handedness-, and IQ-matched adult neurotypical and association with DAT1 and NET (SLC6A2) variants; Secondary Aims:
- To validate the executive functions (EF), sustained attention (SA), intraindividual variability (IIV), visual-spatial memory (VM) as effective neurocognitive endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and adult neurotypical;
- To examine the developmental trajectory and stability of neuropsychological functions and structural and functional connectivity from childhood to adolescence and young adulthood;
- To correlate the data from structural (morphometric, cortical thickness, gyrification, fiber tract integrity) and functional connectivity (rsfMRI), neuropsychology (Executive function, visual-spatial memory, sustained attention, variability), neurophysiology (Stop-signal ERP) and ADHD core symptoms stratifying by the presence of ADHD, presence of DAT1 and NET (SLC6A2) variants, proband-unaffected sibling dyads, and different developmental stages.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ADHD group | – | –Drug-naïve adult ADHD Probands |
| Sibling group | – | –Unaffected Siblings of Drug-naïve Adult ADHD |
| Control group | – | –Age-, sex-, handedness-, and IQ-matched controls without lifetime ADHD or a family history of ADHD |
Who may qualify
- Ages
- 16 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- This 5-year proposal consists of two parts: (1) a 3-year case-control study with unaffected siblings and adult neurotypicals as controls to investigate the brain structural connectivity, functional connectivity, neurophysiological, neuropsychological functioning in 60 probands with ADHD, their unaffected siblings (at least 30 same-sex siblings, n=30~60) and age-, sex-, handedness-, and IQ-matched neurotypicals (n=90~120) with estimated total sample size as at least 180 up to 240. (2) a 2-year follow-up study to repeat the neuropsychological and MRI assessments and to assess electrophysiology related to inhibition controls of 40 adolescents and young adults with childhood diagnosis of ADHD and 40 neurotypicals who had same neuropsychological and imaging assessments in 2010.8-1013.7.
Key inclusion criteria (1 listed)
- Subjects aged 16-30, who have clinical diagnosis of a ADHD according to the DSM-IV and DSM-5 diagnostic criteria, and who have never been treated with medication for ADHD treatment. At least 30 out of 60 subjects have same-sex unaffected siblings.
Key exclusion criteria (1 listed)
- The subjects will be excluded from the study if they meet any of the following criteria: (1) Comorbidity with DSM-IV-TR or DSM-5 diagnoses of autism spectrum disorder, schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, organic psychosis, schizotypal personality disorder, bipolar disorder, depression, severe anxiety disorders or substance use; (2) With neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, and history of craniotomy; (3)With visual or hearing impairments, or motor disability which may influence the process of MRI assessment; and (4) Full-scale IQ lower than 80.
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
Structural neuroimaging
Time frame: 1 day
Using diffusing spectrum imaging (DSI) to assess the structural connectivity in frontostriatal, frontoparietal and other circuitries
1 secondary outcome
Functional connectivity of the brain circuits
Time frame: 1 day
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 2 Sep 2021.
- Derived from this study: PubMed 40527386Chang JC, Lin HY, Gau SS. Age-dependent effects of cumulative methylphenidate exposure on brain structure and symptom amelioration in youth with ADHD: A longitudinal MRI study. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111429. doi: 10.1016/j.pnpbp.2025.111429. Epub 2025 Jun 15.
- Derived from this study: PubMed 36990469Lee CY, Goh JOS, Gau SS. Differential neural processing of value during decision-making in adults with attention-deficit/hyperactivity disorder and healthy controls. J Psychiatry Neurosci. 2023 Mar 29;48(2):E115-E124. doi: 10.1503/jpn.220123. Print 2023 Mar-Apr.
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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 1 inclusion and 1 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 2 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.
What does the primary outcome measure?
Structural neuroimaging (time frame: 1 day). 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 NCT02642068, which also lists 2 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 2 Sep 2021.