Chronic Fatigue Syndrome
Conditions
Keywords
Chronic fatigue syndrome
Brief summary
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.
Detailed description
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.
Interventions
DRUGSodium Oxybate
OTHERplacebo (fresh potable water)
Sponsors
Medical Research Council
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meeting criteria for CFS according to both the revised CDC (Fukuda 5) and Canadian diagnostic systems. * Aged 25-65. * Good grasp of the English language.
Exclusion criteria
* Taking any of the following medication: opioids, tramadol, phenytoin, valproate, ethosuximide, benzodiazepines, zolpidem, zopiclone, zaleplon, antidepressant except \<30mg amitriptyline, or any other medications likely to interact with sodium oxybate or with sleep in the opinion of the investigators. * 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. * Taken alcohol in the 24 hours before each study visit or drugs of abuse in the week before each study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EEG Slow Wave Activity During Sleep | night 1 | Total power in 0.5-4Hz band in microvolts squared per Hertz (uV\^2/Hz) |
| Daytime Sleepiness | Day 2 | time to fall asleep in minutes |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo First Then Sodium Oxybate 7 Patients who meet criteria for CFS according to both the revised CDC (Fukuda 5) and Canadian diagnostic systems. | 7 |
| Sodium Oxybate First Then Placebo 6 Patients who meet criteria for CFS according to both the revised CDC (Fukuda 5) and Canadian diagnostic systems. | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (5 Days) | Physician Decision | 2 | 0 |
| First Intervention (5 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo First Then Sodium Oxybate | Sodium Oxybate First Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 6 / 12 | 5 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Daytime Sleepiness
time to fall asleep in minutes
Time frame: Day 2
Population: All participants who completed the study and whose recordings were adequate
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oxybate | Daytime Sleepiness | 16.95 minutes | Standard Error 0.773 |
| Placebo | Daytime Sleepiness | 15.3 minutes | Standard Error 1.35 |
Primary
Daytime Sleepiness
time to fall asleep in minutes
Time frame: Day 5
Population: All participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oxybate | Daytime Sleepiness | 17.9 minutes | Standard Error 0.9 |
| Placebo | Daytime Sleepiness | 17.2 minutes | Standard Error 1.2 |
Primary
EEG Slow Wave Activity During Sleep
Total power in 0.5-4Hz band in microvolts squared per Hertz (uV\^2/Hz)
Time frame: night 1
Population: All participants who completed the study and whose recordings were adequate
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oxybate | EEG Slow Wave Activity During Sleep | 0.00002653 uV^2/Hz | Standard Error 0.00000406 |
| Placebo | EEG Slow Wave Activity During Sleep | 0.00002257 uV^2/Hz | Standard Error 0.00000339 |
Primary
EEG Slow Wave Activity During Sleep
Total power in 0.5-4Hz band in microvolts squared per Hertz (uV\^2/Hz)
Time frame: night 4
Population: All participants who completed the study and whose recordings were adequate
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oxybate | EEG Slow Wave Activity During Sleep | 0.00003051 uV^2/Hz | Standard Error 0.00000492 |
| Placebo | EEG Slow Wave Activity During Sleep | 0.00001759 uV^2/Hz | Standard Error 0.00000225 |