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A double-blind, placebo-controlled trial of methylphenidate in children with hyperkinetic disorder and moderate-severe learning disabilities
ISRCTN ISRCTN68384912
DOI 10.1186/ISRCTN68384912
ClinicalTrials.gov identifier
EudraCT number
Public title A double-blind, placebo-controlled trial of methylphenidate in children with hyperkinetic disorder and moderate-severe learning disabilities
Scientific title
Acronym HSEN
Serial number at source CT2004-1
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
Lay summary Not provided at time of registration
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).
Countries of recruitment United Kingdom
Disease/condition/study domain Hyperkinetic disorder, mental retardation (intellectual disability)
Participants - 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)
Participants - 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d. Child on neuroleptic medication (must be withdrawn for 2 months prior to trial assessment)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
Anticipated start date 01/06/2004
Anticipated end date 31/05/2007
Status of trial Completed
Patient information material
Target number of participants 180
Interventions 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.
Primary outcome measure(s) Conners parent and teach questionnaires, short form: ADHD and hyperactivity indices
Secondary outcome measure(s) 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)
Sources of funding The Health Foundation
Trial website
Publications 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/22676856
Contact name Dr  Emily  Simonoff
  Address Professor of Child and Adolescent Psychiatry
Child and Adolescent Psychiatry
Institute of Psychiatry
De Crespigny Park
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
  Tel +44 (0)20 7848 5312
  Fax +44 (0)20 7708 5800
  Email e.simonoff@iop.kcl.ac.uk
Sponsor King's College London (UK)
  Address Institute of Psychiatry
De Crespigny Park
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
  Email g.dale@iop.kcl.ac.uk
Date applied 10/03/2006
Last edited 16/01/2014
Date ISRCTN assigned 09/05/2006
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