Neuro-developmental disorders Nervous System Diseases Neuro-developmental disorders
Conditions
Interventions
4 week run in period with sleep hygiene intervention, followed by treatment with either melatonin or placebo.
At the end of 4 weeks (T0), assuming the child continues to fulfil the entry criteria an
wherever possible, this time will remain the same throughout the study. The starting dose will be 0.5 mg and will increase every 7 days through 2 mg and 6 mg up to a maximum of 12 mg, depending upon t
Sponsors
Alder Hey Children's NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current information as of 08/06/2010: 1. Children aged 3 years to 15 years 8 months at screening All other inclusion criteria remain the unchanged. Amended as of 29/04/2008: 1. Children aged 5 years to 15 years 8 months at screening 2. Diagnosis of a neuro-developmental disorder that has been made by a community paediatrician, paediatric neurologist or paediatric neurodisability consultant, categorised as: 2.1. Developmental delay alone 2.2. Developmental delay and epilepsy* 2.3. Developmental delay and autistic spectrum disorder* (ASD) 2.4. Developmental delay with ?other? (?other? is defined as the child having a specific genetic/chromosomal disorder), or 2.5. Any combination of the above 3. Adaptive Behaviour Assessment System (ABAS) questionnaire score with a percentile rank below 7 4. Minimum 5 months history of impaired sleep at screening as defined by: 4.1. Not falling asleep within one hour of 'lights off' or 'snuggling down to sleep' at age-appropriate times for the child**, and/or: 4.2. Less than 6 hours of continuous sleep in three nights out of five 5. Children whose parents are likely to be able to use the actigraph and complete sleep diaries 6. Children who are able to comply with taking the study drug 7. English speaking 8. Children whose parents have completed sleep diaries for an average of 5 out of 7 nights at T0W. * In coding the presence of epilepsy and ASD diagnoses, we will require sight of documentation from relevant services that demonstrate appropriate diagnostic assessments and investigations have been used ** This will be the child'?s usual bedtime (recorded in the sleep diary) based upon the family?s normal routine Initial information at time of registration: 1. Children aged 5 years to 15 years 11 months / < 16 years 2. Diagnosis of a neuro-developmental disorder that has been made by a community paediatrician, paediatric neurologist or paediatric neurodisability consultant, categorised as: 2.1. developmental delay alone 2.2. developmental delay and epilepsy* 2.3. developmental delay and Autistic Spectrum Disorder* (ASD) 2.4. developmental delay with ?other? (?other? is defined as the child having a specific genetic/chromosomal disorder) 3. Vineland assessment score of at least 2 SD below the age standardised reference population mean 4. No plans to commence the following medication: 4.1. Any benzodiazapines 4.2. alimemazine tartrate 4.3. amisulpride (Solian) 4.4. chlorpromazine (Largactil) 4.5. haloperidol (Haldol) 4.6. olanzapine (Zyprexa) 4.7. risperidone (Risperdal) 4.8. sertindole (Serdolect) 4.9. sulpiride (Sulpidil, Sulpor) 4.10. thioridazine (Melleril) 4.11. trifluoperazine (Stelazine) 5. Diagnosis of impaired sleep as defined by: 5.1. not falling asleep within one hour of 'lights off' or 'snuggling down to sleep' at age-appropriate times for the child**, and/or: 5.2. less than 6 hours of continuous sleep in three nights out of five * In coding the presence of epilepsy and ASD diagnoses, we will require sight of documentation from relevant services, that demonstrate appropriate diagnostic assessments and investigations have been used ** This will be the child?s usual bedtime based upon the family'?s normal routine
Exclusion criteria
Exclusion criteria: Current information as of 08/06/2010: 2. Children who have been taking the following medication for less than 2 months: 2.1. Any benzodiazepines 2.2. Amisulpride (Solian) 2.3. Chlorpromazine (Largactil) 2.4. Haloperidol (Haldol) 2.5. Olanzapine (Zyprexa) 2.6. Risperidone (Risperdal) 2.7. Sertindole (Serdolect) 2.8. Sulpiride (Sulpidil, Sulpor) 2.9. Thioridazine (Melleril) 2.10. Trifluoperazine (Stelazine) 4. Current use of sedative or hypnotic drugs, including Choral hydrate, Triclofos, and alimemazine tartrate (Vallergan) (minimum of 14 days washout required) All other exclusion criteria remain unchanged. Amended as of 29/04/2008: 1. Children treated with melatonin within 5 months prior to screening 2. Any plans to commence the following medication: 2.1. Any benzodiazepines 2.2. Alimemazine tartrate (Vallergan) 2.3. Amisulpride (Solian) 2.4. Chlorpromazine (Largactil) 2.5. Haloperidol (Haldol) 2.6. Olanzapine (Zyprexa) 2.7. Risperidone (Risperdal) 2.8. Sertindole (Serdolect) 2.9. Sulpiride (Sulpidil, Sulpor) 2.10. Thioridazine (Melleril) 2.11. Trifluoperazine (Stelazine) 3. Current use of beta blockers (minimum of 7 days washout required) 4. Current use of sedative or hypnotic drugs, including Choral hydrate and Triclofos (minimum of 14 days washout required) 5. Children with a known allergy to melatonin 6. Regular consumption of alcohol (greater than 3 times per week) 7. Children for whom there are suggestive symptoms of Obstructive Sleep Apnoea Syndrome (OSAS) (such as combinations of snoring, gasping, excessive sweating or stopping breathing during sleep), physical signs supportive of OSAS (such as very large tonsils/very small chin), or results of investigations suggesting OSAS (such as overnight pulse oximetry or polysomnography) for which the child should be referred to appropriate respiratory or ENT colleagues for specific assessment and treatment 8. Girls or young women who are pregnant at the time of screening (T-4W) 9. Currently participating in a conflicting clinical study or participation in a clinical study involving a medicinal product within the last 3 months Previous exclusion criteria: 1. Children treated with melatonin within 6 months prior to screening 2. Children whose parents are unlikely to be able to use the actiwatch or complete sleep diaries, or both 3. Children where there may be a problem with major non-concordance with medication 4. Girls or young women who are pregnant at the time of screening (4 weeks prior to randomisation) 5. Currently participating in a conflicting clinical study or participation in a clinical study involving a medicinal product within the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current information as of 08/06/2010: Total night-time sleep Initial information at time of registration: 1. Total night-time sleep 2. Time to sleep onset (sleep latency) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current information as of 08/06/2010: 1. Total night time sleep calculated using actigraphy data 2. Sleep efficiency calculated by (number of minutes spent sleeping in bed/total number of minutes spent in bed) x 100 3. Composite sleep disturbance index scores 4. Daily global measure of parental perception of child?s sleep quality 5. Behavioural problems assessed using Aberrant Behaviour Checklist (ABC) 6. Quality of Life of the parent assessed using the Family Impact Module of the PedsQL™ 7. Level of daytime sleepiness in caregivers assessed using Epworth Sleepiness Scale 8. Number and severity of seizures evaluated using seizure diaries throughout trial follow-up 9. Adverse effects of melatonin treatment assessed weekly between weeks T0W to T12W using ?TESS? (Treatment Emergent Signs and Symptoms) 10. Salivary melatonin concentrations 11. Associations between genetic variants and abnormal melatonin production 12. Sleep onset latency (the time taken to fall asleep) calculated using actigraphy 13. Sleep onset latency (the time taken to fall asleep) calculated using sleep diaries Amended as of 28/04/2008: 1. Total night time sleep calculated using actigraphy data 2. Sleep efficiency calculated by (number of minutes spent sleeping in bed/total number of minutes spent in bed) x 100 3. Composite sleep disturbance index scores 4. Daily global measure of parental perception of child?s sleep quality 5. Behavioural problems assessed using Aberrant Behaviour Checklist (ABC) 6. Attention and vigilance assessed in care-givers using the car game from the DENEM project 7. Attention and vigilance assessed in children using the Go/No go game from the MARS battery 8. Quality of Life of the parent assessed using the Family Impact Module of the PedsQL™ 9. Level of daytime sleepiness in caregivers assessed using Epworth Sleepiness Scale 10. Number and severity of seizures evaluated using seizure diaries throughout trial follow-up 11. Adverse effects of melatonin treatment assessed we | — |
Countries
United Kingdom
Outcome results
None listed