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| [ Print-friendly version ] |
| The use of MElatonin in children with Neuro-developmental Disorders and impaired Sleep; a randomised, double-blind, placebo-controlled, parallel study |
| ISRCTN | ISRCTN05534585 |
| ClinicalTrials.gov identifier | |
| Public title | The use of MElatonin in children with Neuro-developmental Disorders and impaired Sleep; a randomised, double-blind, placebo-controlled, parallel study |
| Scientific title | |
| Acronym | MENDS |
| Serial number at source | HTA 05/14/02 |
| Study hypothesis |
Current information as of 08/06/10:
Compared with placebo, melatonin treatment will increase total sleep duration. Initial information at time of registration: Compared with placebo, melatonin treatment will reduce sleep latency and increase total sleep duration. Please note that, as of 11/05/2009, the anticipated end date has been updated from 31/05/2009 to 30/11/2010. Please note that as of 08/06/10 this record was updated. The trial now has one primary aim as detailed above. All updates may be found in the relevant field with the above update date. As of 17/03/2011 the target number of participants has been corrected from 172 to 114. |
| Lay summary | |
| Ethics approval | Ethics approval received from the North West MREC on the 26th May 2007 (ref: 07/MRE08/43). |
| Study design |
Randomised, double-blind, placebo-controlled, parallel study
|
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Neuro-developmental disorders |
| Participants - inclusion criteria |
Current information as of 08/06/10:
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 |
| Participants - exclusion criteria |
Current information as of 08/06/10:
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 |
| Anticipated start date | 01/05/2007 |
| Anticipated end date | 30/11/2010 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 114 (172 at time of registration) |
| 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 and further consent is provided, the child will be randomised into the study. Each child will be followed up for 12 weeks from date of randomisation, by a combination of home visits, telephone contact and clinic attendance. The active compound (melatonin) and placebo (matching in package and appearance) will be administered at the time that is appropriate to the child’s usual bedtime; 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 the patient’s response to the preceding dose. |
| Primary outcome measure(s) |
Current information as of 08/06/10:
Total night-time sleep Initial information at time of registration: 1. Total night-time sleep 2. Time to sleep onset (sleep latency) |
| Secondary outcome measure(s) |
Current information as of 08/06/10:
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 28/04/08: 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 weekly between weeks T0W to T12W using ‘TESS’ (Treatment Emergent Signs and Symptoms) 12. Salivary melatonin concentrations 13. Associations between genetic variants and abnormal melatonin production Initial information at time of registration: 1. Number and severity of seizures evaluated using seizure diaries throughout trial follow-up 2. Level of concentration and severity of learning difficulties and behaviour problems assessed using the Aberrant Behaviour Checklist (ABC) 3. Motor skills and memory assessed using electronic tests (DENEM project and MARS battery items) completed by care-givers and children 4. Quality of life of care-giver assessed using the Kidscreen-10 index and child assessed using the Family Impact Module of PedsQL™ 5. Adverse effects of melatonin treatment assessed weekly between weeks T0 to T12W using ‘TESS’ (Treatment Emergent Signs and Symptoms) 6. Salivary melatonin concentrations |
| Sources of funding | NIHR Health Technology Assessment Programme - HTA (UK) |
| Trial website | http://www.hta.ac.uk/project/1522.asp |
| Publications | |
| Contact name | Dr Richard Appleton |
| Address |
The Roald Dahl EEG Department
Paediatric Neurosciences Foundation Alder Hey Children's NHS Foundation Trust Eaton Road |
| City/town | Liverpool |
| Zip/Postcode | L12 2AP |
| Country | United Kingdom |
| Tel | +44 (0)151 252 5851 |
| Fax | +44 (0)151 252 5152 |
| Richard.Appleton@alderhey.nhs.uk | |
| Sponsor | Alder Hey Children's NHS Foundation Trust (UK) |
| Address |
c/o Dr Matthew Peak
Director of Research Alder Hey Children's NHS Foundation Trust Eaton Road |
| City/town | Liverpool |
| Zip/Postcode | L12 2AP |
| Country | United Kingdom |
| Matthew.Peak@alderhey.nhs.uk | |
| Date applied | 23/01/2007 |
| Last edited | 17/03/2011 |
| Date ISRCTN assigned | 26/01/2007 |
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| © 2012 ISRCTN unless otherwise stated. | |
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