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Trial registered on ANZCTR


Registration number
ACTRN12615000457549
Ethics application status
Approved
Date submitted
16/01/2015
Date registered
11/05/2015
Date last updated
11/06/2019
Date data sharing statement initially provided
11/06/2019
Date results information initially provided
11/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
An association between changes in the intestinal microbial flora and the alteration of sleep in Chronic Fatigue Syndrome: A pilot open label trial with use of the antibiotic erythromycin
Scientific title
Is the Gram Positive status in Faecal Microbial Flora in Chronic Fatigue Syndrome associated with alterations in sleep/daytime functioning? A pilot open label trial with use of antibiotic Erythromycin.
Secondary ID [1] 285989 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Fatigue Syndrome 293939 0
Condition category
Condition code
Other 294237 294237 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral tablet of Erythromycin 400mg twice daily for 6 days. Participants note in a daily diary if they did not adhere to the treatment regime at any point during the trial.
Intervention code [1] 290965 0
Treatment: Drugs
Comparator / control treatment
nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294041 0
sleep (measured with actigraphy)
Timepoint [1] 294041 0
Day 7, 15, 22
Secondary outcome [1] 312397 0
Mood (Profile of mood states questionnaire)
Timepoint [1] 312397 0
Day 7, 15, 22
Secondary outcome [2] 314428 0
self-reported fatigue levels (Chalder Fatigue Scale)
Timepoint [2] 314428 0
7, 14, 22 days
Secondary outcome [3] 314429 0
subjective sleep quality
Timepoint [3] 314429 0
day 22

Eligibility
Key inclusion criteria
meet CFS criteria according to the Canadian consensus documen; be aged over 18 years; have a gram-positive count that met a predetermined threshold (measured through stool test analysis)
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
currently on antibiotics and/or been on antibiotics for four weeks prior to Baseline phase; been on any non-prescription probiotics for at least 2 weeks prior to Baseline; currently taking any prescription hypnotics (this does not include melatonin); evidence of a sleep disorder (apart from insomnia or hypersomnia); have an Epworth Sleepiness Score >15

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Repeated measures ANOVA; Wilcoxon tests; Spearman's correlations. This is a pilot study so no sample size estimates were performed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 290580 0
Commercial sector/Industry
Name [1] 290580 0
Bioscreen (Aust) Pty Ltd
Address [1] 290580 0
University Drive, Parkville
Victoria, 3052
Country [1] 290580 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
PO Box 14428
Melbourne, Victoria 8001
Country
Australia
Secondary sponsor category [1] 289266 0
Other
Name [1] 289266 0
CFS Discovery
Address [1] 289266 0
90 Mitcham Road, Donvale VIC 3111
Country [1] 289266 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292218 0
Victoria University Human Research Ethics Committee
Ethics committee address [1] 292218 0
PO Box 14428
Melbourne VIC 8001
Ethics committee country [1] 292218 0
Australia
Date submitted for ethics approval [1] 292218 0
Approval date [1] 292218 0
25/05/2011
Ethics approval number [1] 292218 0
11_64

Summary
Brief summary
Recent important discoveries reinforce the idea that CFS is associated with gut flora imbalances. However, the idea that this can have a major effect on sleep and daytime functioning requires further supporting research. This project will determine whether those participants with CFS who, at baseline, are highly gram-positive (determined via stool analysis and indicative of abnormal gut functioning) and respond to antibiotic treatment (such that the amount of gram positive flora is reduced below a certain threshold) also demonstrate significant and ongoing improvements in sleep, daytime activity, mood and self-reported fatigue symptoms.
Eligible participants will follow a baseline, treatment and follow up protocol, across a total of 22 days. The treatment phase involves taking a course of the antibiotic, Erythromycin, for 6 days.
This is an open label pilot research program which aims to determine whether this treatment leads to improvements during treatment and follow up phases, compared to assessments made in the baseline phase. A second Bioscreen stool analysis will also determine whether reduced gram-positive status has been achieved in the gut.
Trial website
Trial related presentations / publications
Jackson ML, Bruck D, Ball M, Butt H, Lewis D. (2013). An association between changes in the intestinal microbial flora and the alteration of sleep in Chronic Fatigue Syndrome: A pilot open label trial with use of the antibiotic erythromycin. Sleep and Biological Rhythms, 11 (Supp 2): 55.

Jackson ML, Bruck D. (2012). Sleep abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A review. Journal of Clinical Sleep Medicine 8(6): 719-728.
Public notes

Contacts
Principal investigator
Name 54154 0
Prof Dorothy Bruck
Address 54154 0
Victoria University
College of Arts
Footscray Park Campus
PO Box 14428
Melbourne, VIC 8001
Country 54154 0
Australia
Phone 54154 0
+613 9919 2158
Fax 54154 0
Email 54154 0
dorothy.bruck@vu.edu.au
Contact person for public queries
Name 54155 0
Dr Melinda Jackson
Address 54155 0
School of Health Sciences
RMIT University
Bundoora, VIC 3083
Country 54155 0
Australia
Phone 54155 0
+613 99257564
Fax 54155 0
Email 54155 0
melinda.jackson@rmit.edu.au
Contact person for scientific queries
Name 54156 0
Dr Melinda Jackson
Address 54156 0
School of Health Sciences
RMIT University
Bundoora, VIC 3083
Country 54156 0
Australia
Phone 54156 0
+613 99257564
Fax 54156 0
Email 54156 0
melinda.jackson@rmit.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Other publications
Have study results been made publicly available in another format?
Yes
Results – basic reporting
Results – plain English summary