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出境医 / 临床实验 / The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With ADHD: A Lipidomic Study

The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With ADHD: A Lipidomic Study

Study Description
Brief Summary:
  1. To identify the difference in the lipidomic profiles between ADHD and controls;
  2. To examine the effects of methylphenidate and atomoxetine on the lipidomic profiles in ADHD, and the relationship between medication-related changes in the lipidomic profiles and medication-related improvements in the behavioral symptoms and neuropsychological functions;
  3. To map medication-related lipidomic biomolecules to their respective metabolic pathways to identify the underlying mechanisms of neuroprotective effects of methylphenidate and atomoxetine.

Condition or disease Intervention/treatment Phase
Attention Deficit Hyperactivity Disorder Drug: Methylphenidate Drug: Atomoxetine Not Applicable

Detailed Description:

Background: Although the efficacy of methylphenidate and atomoxetine in ADHD is well documented in clinical trials, more studies are needed to clarify the neuroprotective effects of these two medications. Lipids exert important neuroprotective effects for optimal brain development and functioning. Previous studies have demonstrated the significant connection between lipid dysregulation and the occurrence of ADHD. In addition, lipid dysregulation is closely related to the abnormal neural activity in individuals with ADHD. In this 3-year prospective project, we will perform a lipidomic analysis of blood before and after treatment with methylphenidate or atomoxetine, in order to identify the biological connections between the neuroprotective effects of medications and pathways of lipid metabolism in children with ADHD.

Subjects and Methods: 70 drug-naïve patients with ADHD, aged 6-18, and 35 matched typically developing controls will be recruited in this project. We will randomly assign the 70 ADHD patients to two groups, 35 in the methylphenidate group and 35 in the atomoxetine group. Within the 12-week treatment period, we will use ADHDRS-IV, SNAP-IV, CBCL, YSR, CGI-ADHD-S, CGI-ADHD-I, SAICA, and Family APGAR-C to assess the improvement in the behavioral symptoms, and CPT and CANTAB to assess the improvement in the neuropsychological functioning. The blood sample will be collected, and we will use mass spectrometry to assess the medication-related change in lipidomic profiles.

Anticipated Results: Using a prospective design, we anticipate that this study will delineate the effects of methylphenidate and atomoxetine on the lipidomic profiles in patients with ADHD. Furthermore, we will conduct pathway analysis to obtain crucial insight to the lipidomic regulation in neurophysiology of children with ADHD. We expect that the findings will increase our understanding of the neuroprotective effects of methylphenidate and atomoxetine in patients with ADHD, and identify the psychopharmacological mechanism of medication effects in ADHD via the pathways of lipid metabolism and regulation.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With Attention Deficit Hyperactivity Disorder: A Lipidomic Study
Estimated Study Start Date : August 1, 2019
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Methylphenidate
The subjects will receive methylphenidate according to their clinical symptoms
 Drug: Methylphenidate
Methylphenidate is a central nervous system stimulant used for the therapy of attention deficit disorder and narcolepsy.
Other Name: Ritalin
Active Comparator: Atomoxetine
The subjects will receive atomoxetine according to their clinical symptoms
 Drug: Atomoxetine
Atomoxetine is a medication used to treat attention deficit hyperactivity disorder (ADHD).[6] Use is only recommended in those who are at least six years old.[6] It is taken by mouth.[6]
Other Name: Strattera
Outcome Measures
Primary Outcome Measures :
  1. ADHD Rating Scale-IV-Parent version: Investigator-Administered and Scored (ADHDRS-IV) [ Time Frame: 12 weeks ]
    The first efficacy measure is the ADHDRS-IV, which is a scale composed of 18 items. The investigator will conduct a semi-structured interview with the parent to evaluate the severity of ADHD symptoms in the past week. ADHDRS-IV is a valid and reliable tool to assess the severity of ADHD symptoms, which has been widely used in pharmacological studies of ADHD in Taiwanese populations. ADHDRS-IV will be administered from visit 1 through visit 5 (baseline-week 12).


Secondary Outcome Measures :
  1. Swanson, Nolan, and Pelham IV scale (SNAP-IV), Parent Form and Teacher Form [ Time Frame: 12 weeks ]
    The SNAP-IV is composed of the ADHD symptoms for the inattention (Items 1 to 9), the hyperactivity/impulsivity (Items 10 to 18), and the oppositional symptoms (Items 19 to 26). SNAP-IV has been proved to be a valid and reliable tool to evaluate the severity of ADHD symptoms. The Chinese SNAP-IV has been used widely in the pharmacological studies on ADHD in Taiwanese populations. SNAP-IV will be administered from visit 1 through visit 5 (baseline-week 12).


Eligibility Criteria
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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Subjects will be recruited in the present project if they meet the following inclusion criteria:

  1. Children or adolescents, between 6 and 18 years of age, must have ADHD based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental disorders, 5th edition.
  2. Their scores of Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) is greater than 4 at baseline.
  3. They have to be medication-naïve. They never receive any medication for the treatment of ADHD.
  4. They and their parents must understand sufficiently to communicate properly with the investigators.
  5. They must have a Full-Scale Intelligence Quotient (FIQ) score greater than 80.
  6. They must keep regular clinic visits and all required tests, including collection of blood sample and neuropsychological testing.
Contacts and Locations

Contacts
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Contact: Chi-Yung Shang 02-23123456 ext 66965 cyshang@ntu.edu.tw

Locations
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Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 110
Contact: Chi-Yung Sang Shang, MDPHD    02-23123456 ext 66965    cyshang@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Chi-Yung Shang Shang, MDPHD Dept of Psychiatry, National Taiwan University Hospital
Tracking Information
First Submitted Date  ICMJE May 2, 2019
First Posted Date  ICMJE May 3, 2019
Last Update Posted Date May 3, 2019
Estimated Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date July 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2019) 		ADHD Rating Scale-IV-Parent version: Investigator-Administered and Scored (ADHDRS-IV) [ Time Frame: 12 weeks ]
The first efficacy measure is the ADHDRS-IV, which is a scale composed of 18 items. The investigator will conduct a semi-structured interview with the parent to evaluate the severity of ADHD symptoms in the past week. ADHDRS-IV is a valid and reliable tool to assess the severity of ADHD symptoms, which has been widely used in pharmacological studies of ADHD in Taiwanese populations. ADHDRS-IV will be administered from visit 1 through visit 5 (baseline-week 12).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2019) 		Swanson, Nolan, and Pelham IV scale (SNAP-IV), Parent Form and Teacher Form [ Time Frame: 12 weeks ]
The SNAP-IV is composed of the ADHD symptoms for the inattention (Items 1 to 9), the hyperactivity/impulsivity (Items 10 to 18), and the oppositional symptoms (Items 19 to 26). SNAP-IV has been proved to be a valid and reliable tool to evaluate the severity of ADHD symptoms. The Chinese SNAP-IV has been used widely in the pharmacological studies on ADHD in Taiwanese populations. SNAP-IV will be administered from visit 1 through visit 5 (baseline-week 12).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With ADHD: A Lipidomic Study
Official Title  ICMJE The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With Attention Deficit Hyperactivity Disorder: A Lipidomic Study
Brief Summary
  1. To identify the difference in the lipidomic profiles between ADHD and controls;
  2. To examine the effects of methylphenidate and atomoxetine on the lipidomic profiles in ADHD, and the relationship between medication-related changes in the lipidomic profiles and medication-related improvements in the behavioral symptoms and neuropsychological functions;
  3. To map medication-related lipidomic biomolecules to their respective metabolic pathways to identify the underlying mechanisms of neuroprotective effects of methylphenidate and atomoxetine.
Detailed Description

Background: Although the efficacy of methylphenidate and atomoxetine in ADHD is well documented in clinical trials, more studies are needed to clarify the neuroprotective effects of these two medications. Lipids exert important neuroprotective effects for optimal brain development and functioning. Previous studies have demonstrated the significant connection between lipid dysregulation and the occurrence of ADHD. In addition, lipid dysregulation is closely related to the abnormal neural activity in individuals with ADHD. In this 3-year prospective project, we will perform a lipidomic analysis of blood before and after treatment with methylphenidate or atomoxetine, in order to identify the biological connections between the neuroprotective effects of medications and pathways of lipid metabolism in children with ADHD.

Subjects and Methods: 70 drug-naïve patients with ADHD, aged 6-18, and 35 matched typically developing controls will be recruited in this project. We will randomly assign the 70 ADHD patients to two groups, 35 in the methylphenidate group and 35 in the atomoxetine group. Within the 12-week treatment period, we will use ADHDRS-IV, SNAP-IV, CBCL, YSR, CGI-ADHD-S, CGI-ADHD-I, SAICA, and Family APGAR-C to assess the improvement in the behavioral symptoms, and CPT and CANTAB to assess the improvement in the neuropsychological functioning. The blood sample will be collected, and we will use mass spectrometry to assess the medication-related change in lipidomic profiles.

Anticipated Results: Using a prospective design, we anticipate that this study will delineate the effects of methylphenidate and atomoxetine on the lipidomic profiles in patients with ADHD. Furthermore, we will conduct pathway analysis to obtain crucial insight to the lipidomic regulation in neurophysiology of children with ADHD. We expect that the findings will increase our understanding of the neuroprotective effects of methylphenidate and atomoxetine in patients with ADHD, and identify the psychopharmacological mechanism of medication effects in ADHD via the pathways of lipid metabolism and regulation.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Attention Deficit Hyperactivity Disorder
Intervention  ICMJE
  • Drug: Methylphenidate
    Methylphenidate is a central nervous system stimulant used for the therapy of attention deficit disorder and narcolepsy.
    Other Name: Ritalin
  • Drug: Atomoxetine
    Atomoxetine is a medication used to treat attention deficit hyperactivity disorder (ADHD).[6] Use is only recommended in those who are at least six years old.[6] It is taken by mouth.[6]
    Other Name: Strattera
Study Arms  ICMJE
  • Experimental: Methylphenidate
    The subjects will receive methylphenidate according to their clinical symptoms
    Intervention: Drug: Methylphenidate
  • Active Comparator: Atomoxetine
    The subjects will receive atomoxetine according to their clinical symptoms
    Intervention: Drug: Atomoxetine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2019) 		105
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2022
Estimated Primary Completion Date July 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subjects will be recruited in the present project if they meet the following inclusion criteria:

  1. Children or adolescents, between 6 and 18 years of age, must have ADHD based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental disorders, 5th edition.
  2. Their scores of Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) is greater than 4 at baseline.
  3. They have to be medication-naïve. They never receive any medication for the treatment of ADHD.
  4. They and their parents must understand sufficiently to communicate properly with the investigators.
  5. They must have a Full-Scale Intelligence Quotient (FIQ) score greater than 80.
  6. They must keep regular clinic visits and all required tests, including collection of blood sample and neuropsychological testing.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Chi-Yung Shang 02-23123456 ext 66965 cyshang@ntu.edu.tw
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03936491
Other Study ID Numbers  ICMJE 201812200MINA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Taiwan University Hospital
Study Sponsor  ICMJE National Taiwan University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chi-Yung Shang Shang, MDPHD Dept of Psychiatry, National Taiwan University Hospital
PRS Account National Taiwan University Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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