The Daily Telegraph reported today on a “new pill that can combat jet lag”. It said that the pill works by mimicking the effects of the ‘sleep hormone’ melatonin and resets the body’s natural sleep rhythm. Trials have shown that the drug reduces the amount of time it takes to fall asleep and helps people to stay asleep for longer. The newspaper claims the pill could be on the market in three years.
The report is based on two randomised controlled trials of the drug tasimelteon. The trials found that tasimelteon improved sleep quality and time spent asleep in healthy people whose sleep pattern had been brought forward by five hours. More research is needed to demonstrate whether these results apply to the treatment of jet lag (where sleep may be advanced or delayed) or for people with non-travel related insomnia.
The journal article about the study gives no indication as to what stage of testing or approval the drug is at now.
Where did the story come from?
Shantha MW Rajaratnam and colleagues from the Harvard Medical School and other institutions in the US and Australia carried out the research. The work was funded by Vanda Pharmaceuticals, who manufacture the drug. The study was published in the peer-reviewed medical journal The Lancet .
What kind of scientific study was this?
This publication was of two randomised controlled trials of the drug tasimelteon (VEC-162). New drugs usually go through different phases of testing before they can be licensed for use in humans. Here, the researchers reported the methods and results from the phase II and III trials of the drug.
Tasimelteon affects melatonin, a hormone produced in the brain that is involved in regulating the daily rhythm of sleeping and waking. The drug works by binding to melatonin receptors in the body. Because increased levels of melatonin are associated with increased sleepiness, synthetic preparations of melatonin can therefore alter sleep times and increase the ability to sleep and time spent asleep. The researchers thought that tasimelteon would reduce sleep disruption and help people to readjust to an appropriate sleep-wake balance.
The research was carried out in two parts. The first study was a phase II trial in which healthy men and women aged 18 to 50 were randomly assigned to receive tasimelteon (32 individuals – randomised to four different doses: 10, 20, 50 or 100mg) or an inactive placebo (eight individuals). People considered to have pre-adapted to an early morning schedule (on the basis of a questionnaire) were excluded. The participants kept to an eight-hour sleep schedule for two weeks before entering the research institution where they then stayed for seven days in a single bed suite. The suite was designed so that the participants were not aware of time, but were instead subjected to a complex pattern of different intensity lighting.
Sleeping times were normal for the first three nights (11pm to 7am) and a placebo drug was given to the participants half an hour before they went to bed. The sleeping period was then brought forward by five hours (6pm to 2am) for the next three nights (treatment nights 1-3). On these days the participants were randomly assigned to receive one of the four doses of tasimelteon or a placebo half an hour before bedtime. The final treatment was followed by a 24-hour observation period.
Sleep was assessed by blinded observers using polysomnography (which records brain waves during sleep), and melatonin concentrations assessed through regular blood samples throughout the trial. The first day of treatment with the drug was of particular interest as this was the night when the most sleep disruption was expected to occur.
The phase III study involved 411 healthy men and women who had a normal eight-hour sleep pattern for at least one week, then a nine-hour sleep pattern the next week before staying one night at the research institute. For this, the participants were randomly allocated to receive either a placebo (103 individuals) or 20, 50 or 100mg of tasimelteon (total 308 individuals) before an eight-hour sleep. Their sleeping period was again brought forward by five hours before their usual bedtime. Sleep data were collected for the single night of sleep in a similar way to that of the phase II study.
For the phase II study, the main outcomes of interest were the efficiency of sleep, which was assessed through polysomnography, and the daily patterns of the sleep hormone melatonin. The phase III study aimed to investigate the time it took for persistent sleep to occur. Waking after falling sleep was a secondary outcome assessed in both studies.
What were the results of the study?
Completion rates were high in both trials and all participants were analysed in the group to which they had been assigned. In the phase II study, tasimelteon increased sleep efficiency compared to placebo. On treatment day one, those taking the placebo had significantly reduced sleep efficiency (by 20%) and total sleep time (by 113mins) compared to the beginning of the study. Those participants taking tasimelteon did not demonstrate significantly reduced sleep efficiency or sleep time compared to baseline.
Compared to placebo, 50mg and 100mg of tasimelteon improved sleep efficiency and total sleep time, and all doses reduced time taken to fall asleep. On treatment days one to three, the alteration in blood melatonin levels to the earlier advanced sleep time was dose dependent, i.e. higher dose of tasimelteon the higher the levels of melatonin.
In the phase III study, all doses of tasimelteon significantly reduced the time before sleep occurred, improved sleep maintenance (i.e. reducing wakefulness after falling asleep), and significantly improved duration of sleep compared with placebo.
Adverse events were similar across all treatment and placebo groups and were mostly related to blood taking.
What interpretations did the researchers draw from these results?
The authors conclude that “after an abrupt advance in sleep time” tasimelteon improves the ability to fall asleep and maintain sleep with an alteration in the daily pattern of melatonin in the body. It is suggested that tasimelteon may be of some benefit to transient insomnia.
What does the NHS Knowledge Service make of this study?
This publication was of two well-designed and conducted randomised controlled trials of the new drug tasimelteon, which demonstrated its effects on sleep when bedtime was brought forward by five hours. The larger of the two trials found that sleep quality and time taken to fall asleep was improved by all doses of tasimelteon, compared to placebo.
These early trials demonstrate that tasimelteon may have a future role in the treatment of jet lag. However, the following points should be kept in mind when interpreting the results:
- The sleep scenario was artificial and may not totally reflect the effects that would be seen after a long-haul flight. In particular, the efficiency of the drug was tested when the sleep time was brought forwards. As tasimelteon appears to promote the action of melatonin and enhances sleep, it would therefore be of no benefit for travel that causes sleep time to be delayed.
- The studies involved a relatively small number of people and greater numbers would be needed to better clarify the efficiency and, in particular, the safety of the drug. All participants in this study were healthy and different results may have been seen had it been given to those with any medical problems. Those with current sleep disorders were also excluded from the trials, so it cannot be assumed that this drug would be appropriate or safe for use in cases of insomnia unrelated to travel.
- As the researchers note, the studies were not large enough to detect differences in subjective measures, e.g. the individual’s perception of sleep and rest, or any alterations in their alertness or performance.
Importantly, the research did not assess if the ‘improvement’ caused by the drug had an impact on other factors, such as performance. Also the effects of the treatment during waking hours, rather than just effects on sleep is an area that needs further investigation.
Sir Muir Gray adds...
The best thing for the environment is not to fly overnight, preventing both climate change and loss of sleep.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Independent, 2 December 2008
The Guardian, 2 December 2008
The Daily Telegraph, 2 December 2008
Links to the science
The Lancet 2008; Early Online Publication December 02