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ADHDNCT04366609

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

An observational study of ADHD, run by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 7 to 12 years
Conditions the study is for
ADHD
What is being tested?
Methylphenidate
Type of treatment
Pill or oral medicine
How many people
207 participants
Where
No sites listed yet
Study dates
1 May 2012to 1 Nov 2017
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 7 to 12 years
  • All sexes
  • No healthy volunteers
  • Child

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.

Who may be able to join

  • 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

Who cannot join

  • 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.
  • Specific additional exclusion criteria for genetic analyses:
Show all 10Show fewer
  • Non-caucasian
  • Lack of DNA
  • Consanguine patients
  • Variants with a minor allele frequency (MAF) above 0.05 or not in Hardy-Weinberg equilibrium

About this study

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.

Read the detailed description

The study has three aims:

  1. Examine the effect of carboxylesterase 1 (CES1) genotype in children with ADHD on the effectiveness and adverse reactions of treatment with MPH.
  2. Study predictors for the short- and long-term outcome in childhood ADHD
  3. Examine the long-term outcome with respect to ADHD symptoms, and impairment in daily functioning in the cohort

The specific aims are to:

  • Describe the treatment response during the first 12 weeks after initiation of IR-MPH treatment, based on weekly clinician- rated ADHD core symptoms, the rate of normalisation/ borderline normalisation of ADHD core symptoms, adverse reactions, daily and social functioning, and measures of sustained attention.
  • Describe the three-year outcome, based on parent rated ADHD core- and behavior symptoms, and level of impairment in daily functioning.
  • Provide information about predictors for outcome after 12 weeks: clinical characteristics at entry (sex, age group, global severity of psychiatric disorder, psychiatric comorbidity, subtype of ADHD diagnoses), and predictors for outcome after three years: sex, age group, baseline severity of ADHD- and behavior symptoms, IQ, parental psychiatric disorder, maternal educational level, and time to treatment response.
  • Determine the end-dose of IR-MPH after 12 weeks of treatment.
  • Systematically sequence the CES1 gene and associate the identified genotypes of this gene with treatment responses, including dosage of IR-MPH
Conditions
ADHD
Being tested
Methylphenidate
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.

  • MethylphenidateDrug

    Also called Medikinet - N06BA04, Motiron - N06BA04

    Treatment with methylphenidate through dose escalation

Study groups in NCT04366609
Study groupRoleWhat they receive
ADHD patientsTreatment 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.
Receives: Drug: Methylphenidate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 0 to 12

Secondary outcomes (5)

  1. Clinical Global Impression Severity scale (CGI-S)

    Psychometric instrument: The clinician-rated CGI-S is a seven-point Likert scale, rated 1 (normal, not ill at all) to 7 (among the most extremely ill patients)A beneficial symptom reduction was defined by a CGI-S score of 1 or 2 (normal, not ill at all or borderline ill).

    Measured: Week 0 and 12

  2. Clinical Global Impression Improvement (CGI-I)

    Psychometric instrument, clinician-rated CGI-I seven-point Likert scale rated from 1 (very much improved) to 7 (very much worse). A beneficial symptom reduction was defined by a CGI-I score of 1 or 2 (very

    Measured: Week 4-8-12

  3. Test of Variables of Attention (TOVA)

    Computerized, continuous performance test, number of commission errors (response to non-target), number of omission errors (non-response to target), the response time in microseconds, and the variability of response time in correct responses to target were measured over the 21.6-minute-long test used as total raw scores.

    Measured: Week 0 and 12

  4. Parent rated ADHD-RS

    Psychometric instrument: Inattention subscale: 9 items, [range 0-27]. Hyperactivity-Impulsivity subscale: 9 items [range 0-27]. Conduct problems subscale: 8 items, [range 0-24]. Higher score, worse outcome.

    Measured: Week 0-4-8-12, year 3

  5. Teacher rated ADHD-RS

    Psychometric instrument: Inattention subscale: 9 items, [range 0-27]. Hyperactivity-Impulsivity subscale: 9 items [range 0-27]. Conduct problems subscale: 8 items, [range 0-24]. Higher score, worse outcome.

    Measured: Week 0-4-8-12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2020
  2. Study start1 May 2012
  3. Primary completion1 Aug 2014
  4. Study completion1 Nov 2017

Resources

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
Cohort
Time perspective
Prospective
Enrolment
207 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04366609
Sponsor's protocol ID
H-B-2009-026
Status last verified
Jan 2012
First submitted
30 Mar 2020
Last updated
29 Apr 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36795232

  • 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.

    PubMed 34673771

Questions about this trial

What is this clinical trial studying?

An observational study of ADHD, run by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital.

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 3 inclusion and 10 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 29 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

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?

Investigator rated ADHD-RS score (time frame: Week 0 to 12). 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 NCT04366609, which also lists 2 linked publications.

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 29 Apr 2020.

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