The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
Discuss the article on the Forums.

UK, London: RECRUITING NOW: SAFFE trial on enhancing slow-wave sleep in CFS using Xyrem

Discussion in 'Active Clinical Studies' started by Sasha, Jun 8, 2015.

  1. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    The MEA just posted (don't know why they're shouting!):

    The description of the study is here:

    https://www1.imperial.ac.uk/departmentofmedicine/divisions/brainsciences/psychopharmacology/saffe/

    It's a test of a pharmacological therapy to improve sleep and see if it helps with daytime functioning.

    Sounds well worth doing - good to support studies that treat ours like an organic condition.
     
    justy, MEMum, catly and 2 others like this.
  2. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    It's MRC funded so I would hope they'd be aware of the issues but if I were able to take part, I'd want to be assured that they're looking at well-defined (CCC or similar) patients.

    Edit: The trial protocol states that they are indeed using the CCC:

    So roll up, roll up...
     
    Last edited: Jun 9, 2015
    justy, MEMum and Scarecrow like this.
  3. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
     
    MEMum and catly like this.
  4. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,823
    They're only referring to it as CFS, so probably Oxford or Fukuda. Useless.
     
    garcia likes this.
  5. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    Not necessarily - and I'd hate a good study to be scuppered because we made a false assumption.

    If anyone is interested in taking part I think they should definitely get in touch with that unit and find out more (and pass it on to the rest of us). If I lived in London and wasn't already on sleep meds, I'd be interested.

    Here's the trial on the clinical trials register:

    https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002969-35/GB#A

    Doesn't give any info about diagnostic criteria but it names the drug and, interestingly, it's Xyrem (sodium oxybate), which others have looked at for ME.

    I'll edit my title.
     
    MEMum and catly like this.
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    8,889
    Likes:
    8,196
    australia (brisbane)
    Sounds interesting, it seems possible that xyrem in the future could be a regular treatment available to the cfsme public.

    i hope this is a sign thst it could be coming to australia.

    Sasha i hope u get in this study and u find this treatment successful .
     
    Sasha likes this.
  7. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    Thanks, heaps, but I don't live in London and I'm already on sleep meds so I wouldn't qualify. Otherwise, I'd be emailing them!

    The fact that they're looking at Xyrem leads me to think that they'll be familiar with the diagnostic issues - Nancy Klimas did a study on Xyrem - but I think it's important to check.
     
    heapsreal and MEMum like this.
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    8,889
    Likes:
    8,196
    australia (brisbane)

    Maybe when the study is finished it might be possible ?
    it would be interesting to know if it works that well in cfsme as well as those of us who have been on sleep meds for awhile.
     
  9. Scarecrow

    Scarecrow Revolting Peasant

    Messages:
    1,903
    Likes:
    5,384
    Scotland
  10. Scarecrow

    Scarecrow Revolting Peasant

    Messages:
    1,903
    Likes:
    5,384
    Scotland
    I spy with my little eye something beginning with CCC:
     
    justy, Sasha and Valentijn like this.
  11. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    Well spotted, @Scarecrow! Here's the whole of that section, and I'll edit my #2 post to reflect that it's CCC.

     
    heapsreal and Scarecrow like this.
  12. charles shepherd

    charles shepherd Senior Member

    Messages:
    2,239
    Likes:
    16,197
    This is one of five research studies that was funded by the MRC following publication of the report from the MRC Expert Group into ME/CFS in which we identified a number of high priority biomedical research subjects, including sleep disturbance.


    Lay summary of the research:

    MR/J002852/1

    PI: Professor David Nutt, Imperial College London

    Title: Can enhancing SWS improve daytime function in patients with CFS?

    Start Date: 01/04/2012

    End Date: 31/03/2013

    Award Amount: £119,999.60

    Lay Summary

    Sleep disturbance is a core symptom of chronic fatigue syndrome (CFS) and has a huge negative impact on daytime function and quality of life. Studies of sleep in the past 10 years have provided evidence that brain mechanisms of sleep regulation, and in particular homeostasis, are disrupted in CFS. Impaired homeostatic mechanisms of sleep result in poor sleep at night and sleepiness and fatigue during the day, contributing to the subjective and objective cognitive impairment seen in these patients. This study will bring together experts in CFS, sleep and psychopharmacology, to study the nature of homeostatic impairment in CFS and its impact on daytime function. We propose to use a pharmacological agent which increases deep restorative sleep (slow wave sleep) which is a marker for homeostatic drive to sleep at night. We will perform a single-dose challenge test in patient with CFS, to ascertain the extent to which this brief and safe pharmacological enhancement of slow wave sleep (and thus of homeostatic mechanisms) will have a significant beneficial impact on daytime impairment. We will include measures of sleepiness, vigilance, memory and subjective well-being. If our results are positive, this will clearly have several potential benefits to CFS sufferers. First, it will underscore the extent to which a major biological function, namely the homeostatic component of the sleep-wake cycle, is impaired in CFS. Second, it will enable us to focus on a specific important brain pathway. Third, it will allow us to evaluate the extent to which patients' daily functions and quality of life are likely to improve following a good night's refreshing sleep. Fourth, our results would direct future major programmes of research into understanding better the underlying sleep disorder in CFS. Finally, the proposed work may suggest potential therapeutic interventions.

    Technical Summary

    Alterations in slow wave sleep (SWS) and slow wave activity (SWA), the most reliable markers of sleep homeostasis, suggest there may be homeostatic dysregulation in CFS. SWS enhancement improves daytime sleepiness and performance on a number of tasks and the detrimental effects of sleep deprivation on performance can be rescued by administering SWS enhancing drugs. We hypothesised that pharmacological enhancement of SWS may lead to improvements in sleep main-tenance and daytime function in CFS patients suffering from non-restorative sleep. This may represent a new avenue for future treatment.

    The objective of the research is to compare aspects of daytime performance, notably sleepiness, memory, subjective well-being and fatigue after a night's sleep in which SWS has been enhanced with sodium oxybate in comparison with placebo. This is a randomised, double-blind, placebo-controlled crossover study in patients with CFS. 24 patients will spend two 20-hr periods in the research centre, separated by at least a week, where they will have their sleep recorded overnight. They will be given oral liquid sodium oxybate (3g) or matching placebo in divided doses; 15 minutes prior to usual bedtime and again after 3 hours. Sleep will be recorded continuously until subjects' usual rise time or after a maximum of 10 hours. The following day, assessments of sleep propensity (MSLT) will be made, by the standard method of creating sleep opportunities every 2 hours and measuring time to fall asleep. Tests of vigilance, memory,

    visual processing, executive function and subjective experience will be made at intervals during the day. Sleep will be scored using standard methods and spectral analysis will be used to obtain measures of microarchitecture. Subject's daily routines will be measured with actigraphy for the entire study duration.

    The results will be published in peer-reviewed journals and more widely in the non-academic community, and will be used to plan future research.
     
    catly, justy, Scarecrow and 1 other person like this.
  13. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    Thanks, @charles shepherd - good to see the MRC responding to priorities in biomedical research for ME.

    For ease of reading, I've broken up those big paras below:

    Lay Summary

    Sleep disturbance is a core symptom of chronic fatigue syndrome (CFS) and has a huge negative impact on daytime function and quality of life.

    Studies of sleep in the past 10 years have provided evidence that brain mechanisms of sleep regulation, and in particular homeostasis, are disrupted in CFS.

    Impaired homeostatic mechanisms of sleep result in poor sleep at night and sleepiness and fatigue during the day, contributing to the subjective and objective cognitive impairment seen in these patients.

    This study will bring together experts in CFS, sleep and psychopharmacology, to study the nature of homeostatic impairment in CFS and its impact on daytime function.

    We propose to use a pharmacological agent which increases deep restorative sleep (slow wave sleep) which is a marker for homeostatic drive to sleep at night.

    We will perform a single-dose challenge test in patient with CFS, to ascertain the extent to which this brief and safe pharmacological enhancement of slow wave sleep (and thus of homeostatic mechanisms) will have a significant beneficial impact on daytime impairment.

    We will include measures of sleepiness, vigilance, memory and subjective well-being. If our results are positive, this will clearly have several potential benefits to CFS sufferers.

    First, it will underscore the extent to which a major biological function, namely the homeostatic component of the sleep-wake cycle, is impaired in CFS.

    Second, it will enable us to focus on a specific important brain pathway.

    Third, it will allow us to evaluate the extent to which patients' daily functions and quality of life are likely to improve following a good night's refreshing sleep.

    Fourth, our results would direct future major programmes of research into understanding better the underlying sleep disorder in CFS.

    Finally, the proposed work may suggest potential therapeutic interventions.

    Technical Summary

    Alterations in slow wave sleep (SWS) and slow wave activity (SWA), the most reliable markers of sleep homeostasis, suggest there may be homeostatic dysregulation in CFS.

    SWS enhancement improves daytime sleepiness and performance on a number of tasks and the detrimental effects of sleep deprivation on performance can be rescued by administering SWS enhancing drugs.

    We hypothesised that pharmacological enhancement of SWS may lead to improvements in sleep main-tenance and daytime function in CFS patients suffering from non-restorative sleep.

    This may represent a new avenue for future treatment.

    The objective of the research is to compare aspects of daytime performance, notably sleepiness, memory, subjective well-being and fatigue after a night's sleep in which SWS has been enhanced with sodium oxybate in comparison with placebo.

    This is a randomised, double-blind, placebo-controlled crossover study in patients with CFS. 24 patients will spend two 20-hr periods in the research centre, separated by at least a week, where they will have their sleep recorded overnight. They will be given oral liquid sodium oxybate (3g) or matching placebo in divided doses; 15 minutes prior to usual bedtime and again after 3 hours.

    Sleep will be recorded continuously until subjects' usual rise time or after a maximum of 10 hours. The following day, assessments of sleep propensity (MSLT) will be made, by the standard method of creating sleep opportunities every 2 hours and measuring time to fall asleep. Tests of vigilance, memory,

    visual processing, executive function and subjective experience will be made at intervals during the day. Sleep will be scored using standard methods and spectral analysis will be used to obtain measures of microarchitecture. Subject's daily routines will be measured with actigraphy for the entire study duration.

    The results will be published in peer-reviewed journals and more widely in the non-academic community, and will be used to plan future research.​
     
    catly and Scarecrow like this.
  14. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    This looks very good - I hope eligible PWME who are in, or can get to London, will put themselves forward for this. Looks like you can both get an insight into your own sleep issues and contribute to some important research at the same time.

    :thumbsup::thumbsup::thumbsup:
     
    Scarecrow likes this.
  15. Scarecrow

    Scarecrow Revolting Peasant

    Messages:
    1,903
    Likes:
    5,384
    Scotland
    @Sasha You know how this a forum for pwME and how we sometimes have difficulty reading stuff and that?

    See that bit that Charles wrote above?

    Start Date:
    01/04/2012

    End Date: 31/03/2013

    :redface::redface::redface:

    Oh, that sleep study! Would they just get on and publish already. Jeez!

    The were 24 patients in the original study and the one you have highlighted is recruiting 12.

    The estimated study completion date of the 12 patient trial was to have been April 2015.

    I wonder if the original study was inconclusive in some way or if they just didn't get the 24 patients they were looking for. I went back to look at my notes from the CMRC in Bristol last September. They talked about the trial set up but not about results. Can it really be that difficult to recruit 24 (or 36) people for a sleep study? I'd do it but I'm nowhere near.
     
    Last edited: Jun 10, 2015
    Valentijn and Sasha like this.
  16. Sasha

    Sasha Fine, thank you

    Messages:
    12,789
    Likes:
    34,217
    UK
    Well indeed, with our problems with 'click' and the WWF and National Car Parks and all.

    I'm a bit confused now...

    @charles shepherd, can you shed any light?

    Anyway, it's clear that they're recruiting PWME (proper CCC ones) for a trial of Xyrem so roll up, folks, and if anyone is capable of reposting that call for participants on FB on any of the other big UK charities' pages, great.
     
    catly and Scarecrow like this.
  17. garcia

    garcia Aristocrat Extraordinaire

    Messages:
    972
    Likes:
    235
    UK
    I was recommended for this study by my specialist (after many years of waiting to be put forward for some kind of trial). However looking at the fine print, you have to spend about 3 weeks in hospital (5 days at a time). No one who has any level of serious impairment / disability (i.e. ME) would voluntarily do that, so I suspect they will end up mostly with the mildest end of the patient spectrum (chronic fatiguers).

    Also Xyrem is potentially very dangerous as it can cause depressed respiration in some people. I haven't taken it myself, but I've taken another similar drug and got depressed respiration. It was not something I would want to go through again.

    I'm all in favour of drug trials. I just wish they would come up with some better drugs to trial!
     
    Sidereal, ukxmrv, catly and 3 others like this.
  18. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    8,889
    Likes:
    8,196
    australia (brisbane)

    My understanding on what i have read from others who have used it is that its a step by step process in working out the dose.

    in my work i have seen many overdoses on ghb and personally haven't seen anyone stop breathing on this but have work mates who have seen this. It seems more risky than benzos. Besides sedation from ghb, vomiting is common but most also have booze onboard. Most overdoses i think occur because of taking it with booze but also because they have no idea of the strength/dose of what they are taking.

    so i think the dangers of severe respiratory depression are greatly reduced by not drinking alcohol at the same time and by using pharma grade med where drug strength is know and dose is gradually increased to find the optimum dose.

    the study involving 5 days a week for 3 weeks doesnt sound practical for many i guess but also could end up feeling the nest after 3 weeks of good sleep??

    I think a couple of nights supervision while sorting the correct dose out would be important .
    do we know how long before study results are published ? Sleep is one of my favorite topics haha
     
    Sasha and justy like this.
  19. justy

    justy Donate Advocate Demonstrate

    Messages:
    5,312
    Likes:
    12,097
    U.K
    I have to say im with Garcia on this one - the stays in hospital alone would be impossible for most with moderate and all with severe, so once again only those with mild M.E will be included - it makes me annoyed that studies cant be designed to take this into account. 5 days at a time on hospital setting? Bright lights? noise? food? chemical cleaners? perfumes of staff? etc etc...
     
    Sidereal, SOC, Snowdrop and 3 others like this.
  20. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,823
    I'm also not particularly excited about the focus on fixing us by resolving sleep problems. It's just overly-simplistic. It might be a bit relevant for a little symptomatic relief in some cases, but that's pretty much it.
     
    Sidereal, SOC, justy and 1 other person like this.

See more popular forum discussions.

Share This Page