A Longitudinal Follow-up Study of Neuroimage and Neuropsychological Endophenotype Study on ADHD

September 1, 2021 updated by: National Taiwan University Hospital
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.

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Aim:

  1. 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:

  2. 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;
  3. 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
  4. 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 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.
293

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 Univeristy 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

15 years to 25 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

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).

Description

Inclusion Criteria:

  • Subjects who received the same MRI and neuropsychological assessments during 2010.8-2015.7(NCT00916851, NCT01682915).

Exclusion Criteria:

  • 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.

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.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Other: Psychiatric diagnosis
Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5
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.
Other: Psychiatric diagnosis
Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5
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.
Other: Psychiatric diagnosis
Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Neuropsychological functions: Continuous Performance Test(CPT)
Time Frame: 1 day
The 4 dimensions of CCPT: focused attention, hyperactivity/impulsivity, sustained attention, and vigilance.
1 day
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.
1 day
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
1 day
Functional connectivity: Single-echo (SE)
Time Frame: 1 day
SE will be used to evaluate functional connectivity.
1 day
Multi-echo (ME) Resting-state fMRI (rsfMRI)
Time Frame: 1 day
rsfMRI will be used to evaluate functional connectivity.
1 day

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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, 2017

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, 2020

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, 2020

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).
September 17, 2018

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.
September 19, 2018

First Posted (ACTUAL)

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.
September 20, 2018

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

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.
  • 201701033RIND

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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