Clinical trial NCT02942225: The Metabolome Profiling and Pathway Analysis of ADHD
Official title: The Metabolome Profiling and Pathway Analysis of ADHD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Attention-deficit/Hyperactivity Disorder
Keywords: Attention-deficit/hyperactivity disorder
metabolomics
neuropsychological deficits
pathway analysis
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2016-10-24
Enrollment: 240
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We plan to recruit 120 ADHD subjects and 120 control subjects.

Brief summary: The purpose of this study is to understand the pathophysiological mechanisms of ADHD, especially the metabolomic pathway related to the behavioral/neuropsychological deficits of ADHD.

To identify specific metabolites that show significant differences between ADHD and control groups, both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry will be performed. In addition, the behavioral measures include ADHDRS-IV, SNAP-IV, CBCL, CGI-ADHD-S, SAICA, and Family APGAR-C. Neuropsychological testing, including CPT and CANTAB, will be performed. Conditional logistic regression and partial least squares discriminant analysis will be applied to identify significant metabolites for ADHD. Pathway enrichment and topology analyses will be conducted to evaluate the regulated pathways.

Detailed description: Because attention deficit hyperactivity disorder (ADHD) is an early onset and long-term impairing disorder with tremendous impact on individuals, families, and societies, detection and diagnosis are very important for ADHD. Current diagnosis of ADHD relies mainly on clinical observation and interview tools that may involve a great subjective variability, and thus the investigation of objective biomarkers for ADHD is warranted. Metabolomics is the study of a biologic process involving all metabolites that are end products of the cellular process in a whole organism. Because metabolites represent the downstream expression of genome, transcriptome, and proteome, metabolomic profiles are more proximal to the behavioral phenotypes of ADHD. Analyzing metabolic differences between children with ADHD and healthy controls will provide insight into underlying disease pathology. To date, there has been no metabolomics study on ADHD. In this 3-year project, the investigators will perform a metabolomics analysis of serum to identify potential biomarkers for the behavioral and neuropsychological deficits of ADHD.

This is a 3-year project. After careful calculation of sample size, the investigators will recruit 120 drug-naïve children with ADHD, aged 7-18, and 120 healthy controls with matched age, sex and BMI. Using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry, serum-based metabolomic profiling will be performed. The behavioral measures include ADHDRS-IV, SNAP-IV, CBCL, CGI-ADHD-S, SAICA, and Family APGAR-C. Neuropsychological testing, including CPT and CANTAB, will be performed. Conditional logistic regression and partial least squares discriminant analysis will be applied to identify significant metabolites for ADHD. Pathway enrichment and topology analyses will be conducted to evaluate the regulated pathways.

Using a matched study design, the investigators anticipate to identify specific metabolites that show significant differences between ADHD and control groups. In addition, results of pathway analysis may offer more biological understanding in explaining the underlying metabolic regulation among children with ADHD. This findings will significantly contribute to the knowledge of the pathophysiological mechanisms of ADHD, especially the metabolomic pathway related to the behavioral/neuropsychological deficits of ADHD.

Eligibility criteria: Inclusion Criteria:

* Subjects without any current or lifetime DSM-V psychiatric disorders based on the K-SADS-E interviews.

Exclusion Criteria:

* Participants who had any past or current medical or neurological illness, who currently took psychotropic medication, or whose intelligence quotient (IQ) score was less than 80 were excluded.

Primary outcomes:
measure: Psychiatric interview
timeFrame: 1 hour
Secondary outcomes:
measure: Spatial working memory
timeFrame: 1.5 hours
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan Univeristy Hospital
Study officials:
affiliation: Dept of Psychiatry, National Taiwan University Hospital
name: Chi-Yung Shang, MD
role: PRINCIPAL_INVESTIGATOR
References: