Attention Deficit Hyperactivity DisorderNCT03679403
A Longitudinal Follow-up Study of Neuroimage and Neuropsychological Endophenotype Study on ADHD
An observational study of Attention Deficit Hyperactivity Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Read more about this study
- Who is it for?
- Ages 15 to 25 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Psychiatric diagnosis
- Type of treatment
- Injection or infusion
- How many people
- 293 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2017to 31 Jul 2020
- 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 15 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: This 3-year follow-up study will repeat the same neuropsychological (CANTAB, CPT) and MRI (T1, T2, DSI, SE- rsfMRI, counting stroop fMRI) assessments at Time 1 and additionally assess electrophysiology (MMN, Gamma ASSR), fMRI (ME rsfMRI, tasks fMRI) and Computerized Neuropsychological Battery (CNB) among 138 probands with ADHD, 61 unaffected siblings, and 135 neurotypicals who had the same neuropsychological and imaging assessments in 2010.8-2015.7(NCT00916851, NCT01682915).
Who may be able to join
- Subjects who received the same MRI and neuropsychological assessments during 2010.8-2015.7(NCT00916851, NCT01682915).
Who cannot join
- Subjects will be excluded from the study if they have (1) neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, or history of craniotomy; and (2) visual or hearing impairments, or motor disability which may influence MRI assessment.
Trial locations and contacts
1 site in 1 country.
About this study
Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Despite many imaging studies on ADHD across countries, only few longitudinal studies investigated the developmental changes of structural and functional brain connectivity and some imaging studies using unaffected sibling design in western countries. There is no published data regarding developmental changes in brain functions assessed by neuropsychology/physiology/image in Asia and Taiwan as well. The ultimate goals of this 3-year project are to identify which neuropsychological, functional and structural connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers) for ADHD based on this follow-up unaffected sibling study design. Due to the limitation of diffusion tensor image (DTI), original analysis of diffusion spectrum image (DSI), and single-echo resting-state functional MRI (SE rsfMRI), the investigators will adopt Mean Apparent Propagator (MAP)-MRI, tract-based autonomic analysis (TBAA) and multi-echo (ME) rsfMRI in this project. With the accomplishment of the following study goals, this study will be the first longitudinal follow-up neuroimaging/physiological endophenotypes study on ADHD using advanced imaging techniques and comprehensive clinical and neurocognitive data.
Read the detailed description
Primary Aim:
- To examine the developmental changes and stability of neuropsychological functions (NFs, assessed by CPT and CANTAB) and structural (morphometric, cortical thickness, gyrification, fiber tract integrity) and functional connectivity (assessed by SE rsfMRI, counting-Stroop fMRI) from childhood to late adolescence and young adulthood; Secondary Aims:
- To validate a wide range of neuropsychological functions (assessed by CPT, CANTAB, CNB), structural and functional connectivity in the frontostriatal (FS), frontoparietal (FP) and other circuitries, and neurophysiological functions (assessed by event-related potential [ERP]: MMN, Gamma ARRS) as effective imaging endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and age-, sex-, and handedness-matched neurotypicals at Time 1 and Follow-up;
- To identify the Time 1 predictors (behavioral symptoms, NFs, and imaging data) for Follow-up neuroimaging data (Morphometric, DSI, rfMRI, task-fMRI, MMN, Gamma ARRS); and
- To correlate all kinds of neurocognitive data and clinical symptoms profiles stratifying by the presence of ADHD, proband-unaffected sibling dyads, and two time points.
Hypothesis The investigators anticipated despite increasing thinning of cortical thickness, microstructural integrity of several targets fiber tracts, and brain activity of target brain regions and improving neuropsychiatric performance from childhood to late adolescence/young adulthood in neurotypicals and probably in ADHD with lower developmental changes slope in ADHD. These changes of unaffected siblings are in the intermediate position between the ADHD probands and neurotypicals. For the endophenotype part, the investigators anticipate that ADHD probands may have a higher level of altered microstructural integrity and decreased brain activity of the FS, FP, other hypothesized fiber tracts/brain networks, deficits in MMN and Gamma, and impaired a wide-ranging NFs than neurotypicals. These differences in the unaffected siblings would be in the intermediate position between ADHD probands and neurotypicals.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Psychiatric diagnosis
- 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.
Psychiatric diagnosisOther
Kiddie Schedule for Affective Disorders \& Schizophrenia (K-SADS) for DSM-5
| Study group | Role | What they receive |
|---|---|---|
| ADHD Probands | Subjects with DSM-IV ADHD who received the same MRI and CANTAB+CPT assessments during 2010.8-2015.7(NCT00916851, NCT01682915) at their age of 8-17 will be reassessed at the estimated age of 15-25. Receives: Other: Psychiatric diagnosis | |
| Unaffected siblings of ADHD | The unaffected siblings received the MRI and CANTAB+CPT assessments during 2013.8-2015.7 (NCT01682915) will be recruited and assessed. Receives: Other: Psychiatric diagnosis | |
| Neurotypicals Follow-up | Subjects without any lifetime diagnosis of DSM-IV ADHD or other psychiatric disorders as the control group of the ADHDFU group around 4-8 years ago when they received the same MRI and neuropsychological assessments during 2010.8-2015.7(NCT00916851, NCT01682915) at their age of 8-17 will be reassessed at their estimated age of 15-25. Receives: Other: Psychiatric diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychological functions: Continuous Performance Test(CPT)
The 4 dimensions of CCPT: focused attention, hyperactivity/impulsivity, sustained attention, and vigilance.
Measured: 1 day
Neuropsychological functions: Cambridge Neuropsychological Test Automated Batteries(CANTAB)
The 4 main cognitive components of CANTAB: Visual Memory, Attention, Working and Planning Memory (Executive Functions), and Decision Making.
Measured: 1 day
Structural neuroimaging: Diffusing spectrum imaging (DSI)
Using a pulsed-gradient spin-echo diffusion EPI(echo planar imaging) sequence with a twice-refocused balanced echo to acquire diffusion-weighted images
Measured: 1 day
Functional connectivity: Single-echo (SE)
SE will be used to evaluate functional connectivity.
Measured: 1 day
Multi-echo (ME) Resting-state fMRI (rsfMRI)
rsfMRI will be used to evaluate functional connectivity.
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 posted20 Sep 2018
- Study start1 Aug 2017
- Primary completion31 Jul 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- 293 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03679403
- Sponsor's protocol ID
- 201701033RIND
- Status last verified
- Sep 2021
- First submitted
- 17 Sep 2018
- Last updated
- 2 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 40527386
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
- A Longitudinal Follow-up Study of Neuroimage and Neuropsychological Endophenotype Study on ADHD
- ClinicalTrials.gov ID
- NCT03679403
- Acronym / sponsor ID
- 201701033RIND
- Conditions
- Attention Deficit Hyperactivity Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 293 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 20 Sep 2018 (actual)
- 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) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Despite many imaging studies on ADHD across countries, only few longitudinal studies investigated the developmental changes of structural and functional brain connectivity and some imaging studies using unaffected sibling design in western countries. There is no published data regarding developmental changes in brain functions assessed by neuropsychology/physiology/image in Asia and Taiwan as well. The ultimate goals of this 3-year project are to identify which neuropsychological, functional and structural connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers) for ADHD based on this follow-up unaffected sibling study design. Due to the limitation of diffusion tensor image (DTI), original analysis of diffusion spectrum image (DSI), and single-echo resting-state functional MRI (SE rsfMRI), the investigators will adopt Mean Apparent Propagator (MAP)-MRI, tract-based autonomic analysis (TBAA) and multi-echo (ME) rsfMRI in this project. With the accomplishment of the following study goals, this study will be the first longitudinal follow-up neuroimaging/physiological endophenotypes study on ADHD using advanced imaging techniques and comprehensive clinical and neurocognitive data.
Detailed description
Primary Aim:
- To examine the developmental changes and stability of neuropsychological functions (NFs, assessed by CPT and CANTAB) and structural (morphometric, cortical thickness, gyrification, fiber tract integrity) and functional connectivity (assessed by SE rsfMRI, counting-Stroop fMRI) from childhood to late adolescence and young adulthood; Secondary Aims:
- To validate a wide range of neuropsychological functions (assessed by CPT, CANTAB, CNB), structural and functional connectivity in the frontostriatal (FS), frontoparietal (FP) and other circuitries, and neurophysiological functions (assessed by event-related potential [ERP]: MMN, Gamma ARRS) as effective imaging endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and age-, sex-, and handedness-matched neurotypicals at Time 1 and Follow-up;
- To identify the Time 1 predictors (behavioral symptoms, NFs, and imaging data) for Follow-up neuroimaging data (Morphometric, DSI, rfMRI, task-fMRI, MMN, Gamma ARRS); and
- To correlate all kinds of neurocognitive data and clinical symptoms profiles stratifying by the presence of ADHD, proband-unaffected sibling dyads, and two time points.
Hypothesis The investigators anticipated despite increasing thinning of cortical thickness, microstructural integrity of several targets fiber tracts, and brain activity of target brain regions and improving neuropsychiatric performance from childhood to late adolescence/young adulthood in neurotypicals and probably in ADHD with lower developmental changes slope in ADHD. These changes of unaffected siblings are in the intermediate position between the ADHD probands and neurotypicals. For the endophenotype part, the investigators anticipate that ADHD probands may have a higher level of altered microstructural integrity and decreased brain activity of the FS, FP, other hypothesized fiber tracts/brain networks, deficits in MMN and Gamma, and impaired a wide-ranging NFs than neurotypicals. These differences in the unaffected siblings would be in the intermediate position between ADHD probands and neurotypicals.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ADHD Probands | – | Other: Psychiatric diagnosisSubjects with DSM-IV ADHD who received the same MRI and CANTAB+CPT assessments during 2010.8-2015.7(NCT00916851, NCT01682915) at their age of 8-17 will be reassessed at the estimated age of 15-25. |
| Unaffected siblings of ADHD | – | Other: Psychiatric diagnosisThe unaffected siblings received the MRI and CANTAB+CPT assessments during 2013.8-2015.7 (NCT01682915) will be recruited and assessed. |
| Neurotypicals Follow-up | – | Other: Psychiatric diagnosisSubjects without any lifetime diagnosis of DSM-IV ADHD or other psychiatric disorders as the control group of the ADHDFU group around 4-8 years ago when they received the same MRI and neuropsychological assessments during 2010.8-2015.7(NCT00916851, NCT01682915) at their age of 8-17 will be reassessed at their estimated age of 15-25. |
Who may qualify
- Ages
- 15 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- This 3-year follow-up study will repeat the same neuropsychological (CANTAB, CPT) and MRI (T1, T2, DSI, SE- rsfMRI, counting stroop fMRI) assessments at Time 1 and additionally assess electrophysiology (MMN, Gamma ASSR), fMRI (ME rsfMRI, tasks fMRI) and Computerized Neuropsychological Battery (CNB) among 138 probands with ADHD, 61 unaffected siblings, and 135 neurotypicals who had the same neuropsychological and imaging assessments in 2010.8-2015.7(NCT00916851, NCT01682915).
Key inclusion criteria (1 listed)
- Subjects who received the same MRI and neuropsychological assessments during 2010.8-2015.7(NCT00916851, NCT01682915).
Key exclusion criteria (1 listed)
- Subjects will be excluded from the study if they have (1) neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, or history of craniotomy; and (2) visual or hearing impairments, or motor disability which may influence MRI assessment.
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 |
|---|---|---|
| Psychiatric diagnosisKiddie Schedule for Affective Disorders \& Schizophrenia (K-SADS) for DSM-5 | Other | ADHD Probands, Neurotypicals Follow-up, Unaffected siblings of ADHD |
Primary outcome
Neuropsychological functions: Continuous Performance Test(CPT)
Time frame: 1 day
The 4 dimensions of CCPT: focused attention, hyperactivity/impulsivity, sustained attention, and vigilance.
Neuropsychological functions: Cambridge Neuropsychological Test Automated Batteries(CANTAB)
Time frame: 1 day
The 4 main cognitive components of CANTAB: Visual Memory, Attention, Working and Planning Memory (Executive Functions), and Decision Making.
Structural neuroimaging: Diffusing spectrum imaging (DSI)
Time frame: 1 day
Using a pulsed-gradient spin-echo diffusion EPI(echo planar imaging) sequence with a twice-refocused balanced echo to acquire diffusion-weighted images
Functional connectivity: Single-echo (SE)
Time frame: 1 day
SE will be used to evaluate functional connectivity.
Multi-echo (ME) Resting-state fMRI (rsfMRI)
Time frame: 1 day
rsfMRI will be used to evaluate functional connectivity.
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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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?
Neuropsychological functions: Continuous Performance Test(CPT) (time frame: 1 day). The study lists 5 primary outcomes in all. 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 NCT03679403, which also lists 1 linked publication.
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.