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

Sasha

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The MEA just posted (don't know why they're shouting!):

MEA on FB said:
COLIN BARTON TELLS ME THAT THIS SLEEP STUDY GROUP AT IMPERIAL COLLEGE LONDON ARE STILL LOOKING FOR VOLUNTEERS WHO HAVE ME/CFS

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.

Imperial College London said:
The SAFFE Study
saffe.png

Slow Wave Sleep And Daytime
Functioning in Chronic FatiguE syndrome


PI: Professor David Nutt

Investigators: Dr Claire Durant, Dr Sue Wilson and Professor B Puri

SAFFE study team: saffe@imperial.ac.uk

About the study
We are looking at the link between sleep and daytime functioning in patients with chronic fatigue syndrome.

People with chronic fatigue syndrome (CFS) commonly describe problems with their sleep, often reporting both daytime sleepiness and unrefreshing sleep during the night, which may impact on daytime functioning. Research suggests that deep slow wave sleep may be altered in CFS.

In the SAFFE study we will investigate if enhancing slow wave sleep during the night can affect day time functioning.

The SAFFE study is being undertaken by the Centre for Neuropsychopharmacology at Imperial College London, and is funded by the Medical Research Council (MRC) of the United Kingdom. It has been approved by London Brent Research Ethics Committee: 13/LO/0882.

Who can take part?
We are currently looking for people who:

  • Have a current diagnosis of chronic fatigue syndrome
  • Are aged between the ages of 25 and 65
  • Have a good grasp of the English language
  • Can take part in a research study at Imperial College London.
What is involved?
If you decide that you would like to take part we will contact you and make sure you are eligible; if so you will need to come for a screening visit. All visits will take place at the NIHR/Wellcome Trust Imperial Clinical Research Facility in the Hammersmith Hospital.

Screening visit: The screening consulatation will take about 2 hours and will be followed by an overnight sleep recording. First we will ask for your consent to take part in the study, check you are suitable based on the study guidelines, and ask you to complete some questionaires. We will then ask you to stay the night to have your sleep monitored.

If you are suitable for the study, you will be asked to attend the research centre for two periods of 5 days from Monday evening until Friday late afternoon, separated by at least a week.

Study visits: Monday afternoon to Friday evening. We will ask you to stay in the Wellcome Research Centre for the majority of the study. You are welcome to leave for a short period of time during some of the days although you will need to stay in the research centre overnight. All your meals and refreshments will be provided.

During the study visits you will be asked to:

  • Take some medication before you go to sleep each night
  • Have your sleep monitored during the night and sometimes during the day
  • Complete some questionnaires and tasks which measure day time functioning and physical fatigue
How do I find out more?
If you would like to find out more, please contact the study team by emailing: saffe@imperial.ac.uk or writing to;

SAFFE study team
Centre for Neuropsychopharmacology
Division of Brain Sciences
Imperial College London
Burlington Danes Building
Hammersmith Hospital campus
160 Du Cane Road
London W12 0NN

Sounds well worth doing - good to support studies that treat ours like an organic condition.
 

Sasha

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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:

SAFFE trial said:
Meeting criteria for CFS according to both the revised CDC and Canadian diagnostic systems

So roll up, roll up...
 
Last edited:

Sasha

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Bill Clayton on MEA FB said:
This is a very useful study to be a part of, run by a lovely team. I took part in April, and although I was deemed unsuitable for the full study, it highlighted other things that are now being dealt with by my GP. If you are able to travel to London to take part, I highly recommend it.
 
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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
They're only referring to it as CFS, so probably Oxford or Fukuda. Useless.
 

Sasha

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They're only referring to it as CFS, so probably Oxford or Fukuda. Useless.

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.
 

heapsreal

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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

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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 .

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

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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.


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.
 

Scarecrow

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They're only referring to it as CFS, so probably Oxford or Fukuda. Useless.
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 spy with my little eye something beginning with CCC:
E.3 Principal inclusion criteria
Meeting criteria for CFS according to both the revised CDC and Canadian diagnostic systems
 

Sasha

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Well spotted, @Scarecrow! Here's the whole of that section, and I'll edit my #2 post to reflect that it's CCC.

SAFFE Trial said:
E.2.1 Main objective of the trial
The principal research question is to determine whether pharmacological enhancement of slow-wave sleep with sodium oxybate improves sleep maintenance and reduces the impact of sleep disruption in chronic fatigue syndrome on daytime function, specifically sleepiness and cognitive function.

E.2.2 Secondary objectives of the trial
The secondary objectives are to determine whether pharmacological enhancement of slow-wave sleep with sodium oxybate in chronic fatigue syndrome is associated with changes in: subjectively rated sleep, sleepiness and mood; neuropsychological functioning; and muscle fatigue.

E.2.3 Trial contains a sub-study
No

E.3 Principal inclusion criteria
Meeting criteria for CFS according to both the revised CDC and Canadian diagnostic systems
Aged 25-65
Good grasp of the English language

E.4 Principal exclusion criteria
Taking medication which interferes with sodium oxybate metabolism including tramadol, phenytoin, valproate, or medication that would interfere with sleep including benzodiazepines, Z hypnotics, antidepressant except <30mg amitryptyline
Current major psychiatric disorder
Unusual sleep schedule (bedtime routines that fall outside 9 p.m. to 10 a.m.; usual time in bed >12 hours)
Pregnancy, lactation or being female and not using reliable contraception
Relevant abnormal clinical findings at screening visit
 

charles shepherd

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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.
 

Sasha

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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.​
 

Sasha

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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

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@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.
Chronic fatigue syndrome (CFS), characterised by chronic disabling fatigue, sleep impairment and other symptoms, is associated with neither a currently identifiable disease process nor major psychiatric illness, and has an estimated prevalence in primary care of 1-2%. Sleep impairment is common in nearly everyone with CFS, with both daytime sleepiness and unrefreshing nighttime sleep reported, and consequent impact on daytime function. It may be that fundamental regulatory processes that control sleep are disturbed in CFS, leading to different effects on sleep and daytime symptoms depending on the subject's prior sleep, daytime routine, medication and other factors. The investigators contacts with patient groups have indicated that patients are generally confident that on days when their sleep is better they perform better in the day. There is growing evidence that deep, slow wave sleep (SWS) is altered in CFS, and this may suggest impairment of build up of sleep pressure during the day.

The investigators wish to investigate whether enhancement of SWS, which is seen after a drug called sodium oxybate, reduces the impact of sleep disruption in CFS on daytime function, specifically sleepiness and mental performance. This is a safe and well-tolerated drug that is licensed for excessive daytime sleepiness (EDS) and cataplexy associated with narcolepsy.

The investigators will study 12 patients diagnosed with CFS using international diagnostic guidelines. The investigators will record overnight sleep with EEG (brainwave) measurement on the 1st and 4th nights of a 4 night period during which sodium oxybate and placebo will be taken nightly, and the investigators will measure next-day sleepiness, mental performance and fatigue, and compare drug and placebo nights.
 
Last edited:

Sasha

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@Sasha You know how this a forum for pwME and how we sometimes have difficulty reading stuff and that?

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.
 

garcia

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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!
 

heapsreal

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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!


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
 

justy

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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...