Treating gut flora imbalances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A pilot open label trial examining sex differences and psychological symptoms.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12614001077651
• Date of registration: 09/10/2014
• Prospective Registration: Yes
• Primary sponsor: CFS Discovery Clinic
• Public title: Treating gut flora imbalances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A pilot open label trial examining sex differences and psychological symptoms.
• Scientific title: Assessing actigraphic sleep efficiency, Profile of Mood States and Rapid Visual Information Processing for antibiotic and probiotic treatment to reduce gut dysbiosis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients with high Streptococcus: Comparison between sexes.
• Date of first enrolment: 29/07/2015
• Target sample size: 40
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12614001077651.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Efficacy;
• Phase: Not Applicable

Countries of recruitment

Australia

Contacts

• Name: Miss Amy Wallis

• Name: Prof Dorothy Bruck

Key inclusion & exclusion criteria

Inclusion criteria: Participants will be patients who have voluntarily presented or been referred to CFSDC. Prospective participants will be:
- aged above 18 years
- meet the CCC diagnostic criteria for CFS (Carruthers et al., 2003). The CCC is more commonly used to make a diagnosis of ME/CFS in clinical practice.
- have higher than normal Streptococcus bacteria count levels as indicated by pathology testing (Bioscreen FMA). High levels of Streptococcus are determined by a viable count reference range above 3.00 x 10(exponent 5) cfu/gm and greater than 5% distribution within aerobic microorganisms. Normal levels are below the aforementioned count and distribution levels.
- refrain from taking any other antibiotics for 4 weeks prior and throughout the study period.
- refrain from taking any other probiotics for 2 weeks prior and throughout the study period.
- agree to refrain from substantially altering their current diet and intake of prescription medication or over-the-counter supplements throughout the 6 week study period - or notify the researchers of any changes required at the time of the change.

We will be recruiting equal proportions of male (n = 20) and female (n = 20) participants to evaluate sex-specific treatment responses.
Exclusion criteria: Exclusion criteria are individuals with known adverse reactions to antibiotic/probiotic treatment, concurrent contraindicative medication, or significant comorbid physical or psychiatric illnesses that prevent appropriate completion of the study.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Other - Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome;
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Intervention(s)

The Active Treatment Protocol will be combined antibiotic and probiotic therapy for 4 weeks duration.
Week 1 = Erythromycin (EES-400mg) - 2 x daily oral capsules
Week 2 = Pro4 - 50 D-Lactate Free multistrain probiotic (2 x daily oral capsules)
Week 3 = Erythromycin (EES-400mg) - 2 x daily oral capsules
Week 4 = Pro4 - 50 D-Lactate Free multistrain probiotic (2 x daily oral capsules)

Each capsule of Pro4 - 50 D-Lactate Free multistrain contains:
Lactobacillus rhamnosus 25 billion CFUs
Bifidobacterium lactis 15 billion CFUs
Bifidobacterium breve 5 billion CFUs
Bifidobacterium longum 5 billion CFUs
Total CFU Count: 50 billion


Treatment response and compliance will be monitored by weekly phone calls throughout the intervention phase and assessed through participant self-report questions at the end of the study. The second Bioscreen Faecal Microbial Analysis will provide information about any gut flora changes and will be used in conjunction with participant's self-reported treatment adherence.


This treatment protocol is in accordance with current practice at CFSDC. The use of Erythromycin has been TGA approved for Streptococcal infection whilst not specifically indicated for treatment of ME/CFS populations. EES used in this study is not aimed to eradicate faecal streptococcus; but prophylactically to suppress the index organism.

Primary Outcome(s)

Mean Rapid Visual Information Processing (RVP) on CANTAB[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean actigraphic sleep efficiency score[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Profile of Mood Scale (POMS) mean scores[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Secondary Outcome(s)

Mean scores on Controlled Oral Word Association Test (COWAT)[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on Weschler Memory Scales (WMS-IV) Logical Memory Subscale[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Depression, Anxiety and Stress Scale (DASS-21) mean scores[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Symptom Severity and Symptom Hierarchy Profile scores[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on Spatial Working Memory (SWM) on CANTAB[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

The Multidimensional Fatigue Inventory (MFI-20) mean scores[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Bioscreen Fecal Microbial Analysis results[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on Attention Switching Task (AST) on CANTAB[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on Paired Associate Learning on CANTAB[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on Rey Auditory Verbal Learning Test (RAVLT)[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on the Brain Fog subscale of the Multiple Fatigue Types Questionnaire[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on the Insomnia Severity Index (ISI)[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Subjective sleep diary rating of sleep quality and wakefulness[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

The Mood Adjectives checklist mean scores[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Mean scores on the Pittsburgh Sleep Quality Index (PSQI)[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention)]

Urinary D-lactate levels[At baseline and post-intervention (week 5 after conclusion of the 4 week intervention).]

Secondary ID(s)

Nil

Source(s) of Monetary Support

Bioscreen Specialist Medical Testing Laboratories

Victoria University College of Arts (Psychology)

Secondary Sponsor(s)

Bioscreen Specialist Medical Testing Laboratories

Ethics review

Status: Approved
Approval date:
Contact:

Victoria University Human Research Ethics Committee