The Relationship Between CES1 Genotype and Methylphenidate Response in Children With ADHD - INDICES Work Package 6

NCT04366609 | Completed FDA Drug

• 1 other identifier: H-B-2009-026
• Study Type: observational
• Target: 207
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective observational study of a cohort of children diagnosed with Attention Deficit Hyperactive Disorder (ADHD) and followed with weekly assessments during the first 12 weeks of Methylphenidate (MPH) treatment, and after three years. The overall aim is to gain knowledge in order to develop guidelines for more individualized treatments with (MPH), obtain a better drug response, and reduce the risk of adverse reactions, in order to improve adherence and long-term outcome.

Conditions

ADHD

Outcome Measures

Primary Outcomes (1)

• Investigator rated ADHD-RS score

  Psychometric instrument: 18 item clinician rated; Inattention subscale: 9 items, \[range 0-27\]. Hyperactivity-Impulsivity subscale: 9 items \[range 0-27\], evaluated on a four-point Likert scale from 0 (none = never or rarely) to 3 (severe = very often). Higher score, worse outcome. Normalisation: T-score\<60, Borderline normalisation: T-score 60-70.

  Week 0 to 12

Secondary Outcomes (5)

• Clinical Global Impression Severity scale (CGI-S)

  Week 0 and 12

• Clinical Global Impression Improvement (CGI-I)

  Week 4-8-12

• Test of Variables of Attention (TOVA)

  Week 0 and 12

• Parent rated ADHD-RS

  Week 0-4-8-12, year 3

• Teacher rated ADHD-RS

  Week 0-4-8-12

Other Outcomes (12)

• Weiss Functional Impairment Rating Scale - Parent version (WFIRS-P).

  Week 0 and 12, year 3

• Barkley's Stimulant Side Effect Rating Scale (BSSERS-C)

  Week 0 to 12

• Child Behaviour Check List (CBCL)

  Week 0

Study Arms (1)

ADHD patients

Treatment of young ADHD patients with methylphenidate following The Danish guidelines, which are similar to The NICE guidelines: use of an initial low oral dose of MPH and an up-titration period of at least 4 weeks, until no further effect is measured on a standard ADHD rating scale, or the appearance of intolerable ARs, or a maximum dose of 2.1 mg/kg/day.

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

Treatment with methylphenidate through dose escalation

Also known as: Medikinet - N06BA04, Motiron - N06BA04

ADHD patients

Eligibility Criteria

• Age: 7 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

207 MPH naïve boys and girls aged 7-12 years with a recent ICD-10 diagnosis of hyperkinetic disorder (F90.0-90.9) or attention deficit disorder without hyperactivity (F98.8) and clinical indication for treatment with IR-MPH. Patients referred to the Child and Adolescent Mental Health Centre, Mental Health Services (Capital Region of Denmark) in the period from 1st of May 2012 to 1st August 2014, and who were suspected of having ADHD were consecutively screened for study eligibility.

You may qualify if:

• MPH naïve
• recent ICD-10 diagnosis of hyperkinetic disorder (F90.0-90.9) or attention deficit disorder without hyperactivity (F98.8)
• clinical indication for treatment with IR-MPH

You may not qualify if:

• mental retardation (ICD-F70.X or IQ \< 70)
• previous treatment with drugs metabolised by carboxylesterase 1 (CES1)
• severe comorbid psychiatric or somatic disease that resulted in contraindication for treatment with MPH
• language barriers
• lack of informed consent.
• Non-caucasian
• Lack of DNA
• Consanguine patients
• Variants with a minor allele frequency (MAF) above 0.05 or not in Hardy-Weinberg equilibrium

Sponsors & Collaborators

• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: lead
• Copenhagen University Hospital, Denmark: collaborator

Related Publications (2)

• Houmann TB, Kaalund-Brok K, Clemmensen L, Petersen MA, Plessen KJ, Bilenberg N, Verhulst F, Jeppesen P; INDICES. Early treatment response as predictor of long-term outcome in a clinical cohort of children with ADHD. Eur Child Adolesc Psychiatry. 2024 Feb;33(2):357-367. doi: 10.1007/s00787-023-02158-z. Epub 2023 Feb 16.

  PMID: 36795232 DERIVED

• Kaalund-Brok K, Houmann TB, Hebsgaard MB, Lauritsen MG, Lundstrom LH, Gronning H, Darling L, Reinert-Petersen S, Petersen MA, Jepsen JRM, Pagsberg AK, Plessen KJ, Rasmussen HB, Jeppesen P; INDICES. Outcomes of a 12-week ecologically valid observational study of first treatment with methylphenidate in a representative clinical sample of drug naive children with ADHD. PLoS One. 2021 Oct 21;16(10):e0253727. doi: 10.1371/journal.pone.0253727. eCollection 2021.

  PMID: 34673771 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA from saliva collected in the Oragene OG-250 DNA kit (DNA Genotek Inc., ON, Canada).

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pia Jeppesen, PhD, MD

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  PRINCIPAL INVESTIGATOR

• Tine B Houmann, MD

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 29, 2020
• Study Start: May 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: November 1, 2017
• Last Updated: April 29, 2020

Record last verified: 2012-01

Data Sharing

• IPD Sharing: Will not share