Condition category
Mental and Behavioural Disorders
Date applied
10/03/2006
Date assigned
09/05/2006
Last edited
16/01/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Emily Simonoff

ORCID ID

Contact details

Professor of Child and Adolescent Psychiatry
Child and Adolescent Psychiatry
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom
+44 (0)20 7848 5312
e.simonoff@iop.kcl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CT2004-1

Study information

Scientific title

Acronym

HSEN

Study hypothesis

1. What is the efficacy of methylphenidate, under conditions of individual dose optimization, in reducing the symptoms of attention deficit hyperactivity disorder (ADHD) among children with moderate and severe learning disabilities?
2. What is the adverse effects profile associated with methylphenidate treatment amongst children with learning disabilities and which children are at greater risk of developing side effects?
3. What are the predictors of good versus poor responders to treatment? In particular:
a. Are those with severe as opposed to moderate learning disabilities less likely to show a good response?
b. Presence of autistic symptoms

Ethics approval

South East Multicentre Research Ethics Committee: MREC 04/01/013

Study design

Randomized controlled trial stratified for severity of learning disability (30-49 versus 50-69).

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Hyperkinetic disorder, mental retardation (intellectual disability)

Intervention

180 children between ages 7 and 15 years with moderate-severe learning disability and hyperkinetic disorder will be invited to take part in a randomized double-blind trial of methylphenidate versus placebo lasting 16 weeks. Medication dosage for methylphenidate will be individually optimized, balancing reduction in hyperkinetic symptoms against side effects. Three dose levels of immediate release medication will be tried, corresponding to 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg daily dose in three divided doses (with the three doses corresponding to 40% in the morning, 40% at lunchtime and 20% after school of the total daily dose). Selection of optimal dose will be based on adverse effects and behavioural response. Treatment response will be determined by comparing baseline behaviour with that at 16 weeks. At the end of the 16 weeks, children will be unblended. Those receiving placebo will have the opportunity to commence active medication with the same dose titration method. Those receiving active medication may continue in an open-label trial, with the possibility of an increase in dose up to 2.0 mg/kg if warranted based on adverse effects and behavioural response. The trial will end at 50 weeks post randomization. Primary outcome points are 16 and 50 weeks, with additional measures wherever possible at 8, 12, 26 and 38 weeks. Ascertainment of research subjects occurs via two arms: clinical referral and population screening.

Not part of treatment trial but interventions:
A behavioural manual (written by the team) is given to all families at the time of eligibility assessment.
Where children have sleep problems, their parents are given a manual on manging sleep problems (standard manual written by Paul Montgomery).
Where sleep problems are ongoing, children may be given melatonin, commencing with 4 mg dose and continuing in weekly 3 mg increments up to 8 mg.

Intervention type

Drug

Phase

Not Specified

Drug names

Methylphenidate

Primary outcome measures

Conners parent and teach questionnaires, short form: ADHD and hyperactivity indices

Secondary outcome measures

1. Adverse events (other behaviours questionnaire plus any others noted)
2. Aberrant behaviour questionnaire
3. Quality of Life (Cadfield)
4. Parental Resport on Neuropsychiatric Symptoms (PONS)

Overall trial start date

01/06/2004

Overall trial end date

31/05/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosis of International Statistical Classification of Diseases and Related Health Problems - tenth revision (ICD-10) hyperkinetic disorder
2. Full-scale IQ 30-69 or age equivalent estimate
3. Living in catchment area of one of the participating centres
4. Child in stable care situation
5. Child regularly attending school (more than 75% of last school term)

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

180

Participant exclusion criteria

1. Child currently in another trial of psychoactive medication
2. Household member with recent diagnosis of substance abuse
3. Severe limitation of child's mobility
4. Presence of a degenerative disorder
5. Medical conditions precluding methylphenidate as treatment of first choice, including:
a. Poorly controlled or uncontrolled epilepsy
b. Presence of tics or Tourette disorder
c. History of psychotic, bipolar or severe obsessive compulsive disorder
d. Child on neuroleptic medication (must be withdrawn for 2 months prior to trial assessment)
e. History of intolerance to stimulant medication
f. Child poses a significant risk of suicidal or homicidal behaviour
6. Another child in the family/household already enrolled in this study
7. Ongoing child protection concerns

Recruitment start date

01/06/2004

Recruitment end date

31/05/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Professor of Child and Adolescent Psychiatry
London
SE5 8AF
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom
g.dale@iop.kcl.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

The Health Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/22676856

Publication citations

  1. Results

    Simonoff E, Taylor E, Baird G, Bernard S, Chadwick O, Liang H, Whitwell S, Riemer K, Sharma K, Sharma SP, Wood N, Kelly J, Golaszewski A, Kennedy J, Rodney L, West N, Walwyn R, Jichi F, Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability., J Child Psychol Psychiatry, 2013, 54, 5, 527-535, doi: 10.1111/j.1469-7610.2012.02569.x.

Additional files

Editorial Notes