Details of HTA project in progress
Last updated: 31 August 2010 - Next update due: 7 September 2010
Research type: |
Primary Research (e.g. trial) |
Project title: |
The use of MElatonin in children with Neuro-Developmental disorders and impaired sleep; a randomised, double-blind, placebo-controlled, parallel Study (MENDS) |
Project ref: |
05/14/02 |
Cost: |
£1,000,694 |
Chief Investigator : |
Dr Richard Appleton, Consultant Paediatric Neurologist, Roald Dahl EEG Department, Alder Hey Children's NHS Foundation Trust |
Start Date: |
May 2007 |
Estimated date of publication in HTA journal series: |
Mid 2012. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
The management of sleep problems in children with learning difficulties is often less than ideal because the drugs used have unwanted side-effects or behaviour management is very difficult to arrange. Melatonin is a drug which may improve sleep in these children and it seems to have far fewer side-effects than the other drugs used. The question is, how effective and safe Melatonin is in improving night-time sleep in children with developmental or learning difficulties? The best way to accurately answer this question is to compare the Melatonin to an inactive treatment (called a 'placebo' or 'dummy') in a double-blind randomised controlled trial (or 'RCT'). This means that upon study entry the treatment will be assigned by chance and neither the caregiver nor doctor will know whether it is Melatonin or placebo which is received. 172 children, aged 5 to 18 years, boys and girls, will be studied. The study should be completed within two years. The only ethical issue is comparing Melatonin with a placebo instead of with an active drug. However, there is no other single, 'standard' drug that is used to treat disturbed sleep in children; the other drugs that can be used all have side-effects. The doctors doing the study and the families would then know which drug their child is receiving and this would un-blind the trial. As a result, the study would not be able to answer the question - whether Melatonin is effective in improving sleep. The study will look at two main outcomes. These are total night-time sleep and the time taken to fall asleep. The study will also measure how many times the children wake up during the night. These outcomes will be measured using nightly sleep diaries, a simple device worn at the wrist (like a watch) and questionnaires. Some questionnaires will also be used to assess quality of life in the children and their families. The research team is qualified to undertake this research as it includes all the specialties and skills needed for the study, has considerable experience in caring for children with developmental problems and the use of Melatonin and is active in health research. The costs of the study are justified because the study has to be large, involving many centres and undertaken using both subjective and objective outcomes. The Melatonin and placebo are to be provided at no cost, however equipment and research nurses are necessary to ensure that the study can be carried out successfully and answer the research question. |
Project Abstract: |
Melatonin, a natural substance produced by the pineal gland, is responsible for regulating the circadian rhythm, including sleep-wake cycling. Production of melatonin is increased in the evening and suppressed by light, making melatonin a hormonal signal of darkness. Children with neurological and/or developmental disorders have a higher prevalence of sleep disturbances and there is considerable evidence that chronic sleep-wake disorders of children with neuro-developmental disorders are associated with an inability to synchronise their sleep-wake cycle generating system with environmental zeitgebers, resulting in abnormal melatonin secretion. Usually far more difficult to treat than their 'normally' developing peers, sleep disorders in children with neurological and/or developmental disorders may result in additional learning and behavioural problems. Disturbed sleep, specifically discontinuous sleep with frequent awakenings throughout the night, commonly results in disturbed sleep in their parents and siblings with secondary detrimental effects on the family - physically, emotionally and socially - and if chronic, even on their ability to continue in employment or further education. Chronic sleep disturbance of multiply disabled children are a frequent cause of families giving up their care. Behavioural approaches used in improving sleep are difficult to apply, time-consuming and usually require skilled and scarce manpower. Treatment with commonly-used hypnotic or sedative drugs is often ineffective and can result in both side-effects and tolerance, and may even be contraindicated in certain clinical situations. Following early results suggesting that melatonin appears to be effective in both reducing the time it takes children to fall asleep (time to sleep onset or sleep latency) as well as increasing the total duration of continuous sleep throughout the night, together with the observation that melatonin appeared to have neither short- nor long-term side-effects, it is increasingly used in open studies, and even in routine clinical practice, for the treatment of sleep disorders of children with a range of neurological disabilities and disorders. However, all of these studies have been non-randomised and anecdotal and the objective of this trial is to confirm (or refute) that immediate release of melatonin is beneficial to placebo in improving total duration of night-time sleep and can reduce sleep latency in children with neuro-developmental problems. |
MeSH* index primary terms: |
DEVELOPMENTAL-DISABILITIES Q-etiology; DEVELOPMENTAL-DISABILITIES Q-psychology; SLEEP-DISORDERS Q-etiology; SLEEP-DISORDERS Q-psychology; MELATONIN Q-secretion |
MeSH* index secondary terms: |
HUMANS; RANDOMIZED-CONTROLLED-TRIAL; DOUBLE-BLIND-METHOD; CLINICAL-TRIAL; CHILD-PRESCHOOL; CHILD; ADOLESCENT |
NRR* number, if applicable: |
N0484189147 (*National Research Register). The National Research Register was a public database of ongoing and recently completed research projects funded by, or of interest to, the United Kingdom's National Health Service (NHS). It is now an archive of projects from early 2000 to September 2007. Search the NRR archive. |
ISRCTN* number: | ISRCTN 05534585 (*International Standard Randomised Controlled Trial Number) URL of this project on the Controlled Trials Website: http://www.controlled-trials.com/ISRCTN05534585 |
Project Protocol: |
Project protocol (pdf format, 2307 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1522 |
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