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
-
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.