SWS And Daytime Functioning in Chronic FatiguE Syndrome (SAFFE) (SAFFE)

Slow-wave Sleep and Daytime Functioning in Chronic Fatigue Syndrome: Effects of Sodium Oxybate

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.

Study Overview

• Status: Completed
• Conditions: Chronic Fatigue Syndrome
• Intervention / Treatment: Drug: Sodium Oxybate; Other: placebo (fresh potable water)

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0NN
    • Wellcome CRF, Imperial College, Hammersmith Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo first, then sodium oxybate; Subjects received a single dose of placebo comparator (fresh potable water) at bedtime on 4 nights during an inpatient stay of 5 days in the research centre. This was followed by an interval of at least 2 weeks. They were then admitted again and received a single dose of sodium oxybate (3.0g as liquid) at bedtime for 4 nights	Drug: Sodium Oxybate; Other Names: Xyrem; Other: placebo (fresh potable water)
Experimental: Sodium oxybate first, then placebo; Subjects received a single dose of sodium oxybate (3.0g as liquid) at bedtime on 4 nights during an inpatient stay of 5 days in the research centre. This was followed by an interval of at least 2 weeks. They were then admitted again and received a single dose of placebo comparator (fresh potable water) at bedtime for 4 nights	Drug: Sodium Oxybate; Other Names: Xyrem; Other: placebo (fresh potable water)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG Slow Wave Activity During Sleep	Total power in 0.5-4Hz band in microvolts squared per Hertz (uV^2/Hz)	night 1
EEG Slow Wave Activity During Sleep	Total power in 0.5-4Hz band in microvolts squared per Hertz (uV^2/Hz)	night 4
Daytime Sleepiness	time to fall asleep in minutes	Day 2
Daytime Sleepiness	time to fall asleep in minutes	Day 5

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Medical Research Council
• Investigators: Principal Investigator: David Nutt, DM FRCPsych, Imperial College London

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: October 27, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Chronic fatigue syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Syndrome; Fatigue; Fatigue Syndrome, Chronic; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Sodium Oxybate
• Other Study ID Numbers: SAFFE2012; 2012-002969-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No