Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001150932
Ethics application status
Approved
Date submitted
18/08/2020
Date registered
3/11/2020
Date last updated
3/11/2020
Date data sharing statement initially provided
3/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating potential biomarkers in Myalgic Encephalomyelitis Chronic Fatigue Syndrome (MECFS) patients
Scientific title
Cytokine (proinflammatory/anti-inflammatory) analysis in Myalgic Encephalomyelitis Chronic Fatigue Syndrome (MECFS) patients: A Two Phase Design. Assessing differences in cytokine levels across two time points.
Secondary ID [1] 302066 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MECFS2PD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
A diagnosis of Myalgic Encephalomyelitis Chronic Fatigue Syndrome 318663 0
Condition category
Condition code
Other 316683 316683 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Samples will be collected at two time-points within a 12 month period, but the time between these two points will be a minimum of 1 month, but within 12 months (determined by the experience of a subjective 'crash'. The baseline assessment will require a series blood samples which requires approximately 55 ml for baseline and the cytokine assessment. Any unused portion of these samples will be stored for future research studies. The second occasion will require less blood to compare with the first (36 ml). Blood samples will be collected by a nurse who will also administer the questionnaires. Some questionnaires can be completed online (taking approximately 1 hour). Each study visit is expected to take approximately 1 hour. The following three questionnaires will be used as part of the interview: Hamilton Depression Scale, Hamilton Anxiety Scale and the General Physical Activity Questionnaire (administered by the nurse interviewer) measured during the visit. Becks Depression Inventory, Flinders Sleep Questionnaire which are self administered will be completed by the participant within a week of the blood test. Then other self completion questionnaires include the DePaul Symptom Questionnaire (DSQ-2), Revised Fibromyalgia Impact Questionnaire, Chronic Fatigue & Fibromyalgia Symptom checklist. We will also ask for a list of Current Medications, and List of Current Supplements. Additionally, we will take bio-metric measures such as your weight, height, blood pressure, and waist hip ratio. Timing: All samples will be taken in a condition of fasting from midnight the night before, and collected between 8am and 10am to suit participant. The questionnaires will be completed at both time points described earlier (when subjectively well, and during a subjective crash). The sleep monitoring will only occur once only as part of the baseline assessment. A crash will be a subjective experience expressed by the participant whereby they feel significantly worse than their usual level of functioning. There is no subset of participants. All participants will be asked to undergo a sleep monitoring test which involves wearing a monitor overnight. This will be a singular assessment as part of the baseline within a week of the initial samples and are an optional part of the research, which we anticipate most participants will be interested in completing. Symptom data collected on the app will be a simple list of common MECFS symptoms described in the International Consensus Criterion. The length of time the app is used for is an optional type of monitoring of symptoms, but for no longer than the period of involvement in the study, i.e. maximum 12 months. Symptoms to monitor will be selected by participants i.e. anything between 5 and 21 common symptoms such as fatigue, headaches, and pain levels. A stool sample and a urine sample will be requested to collect as part of our of collection for future research. This is optional.
Intervention code [1] 318365 0
Diagnosis / Prognosis
Comparator / control treatment
A control group are healthy participants who do not have any current illness and have never been diagnosed with MECFS. We will take the second set of samples at a period greater than 2 months at a time convenient for the participant but less than 12 months. This will allow for variation in time, similar to the person with MECFS.
Control group
Active

Outcomes
Primary outcome [1] 324811 0
This will be a measurement of cytokines in ng/ml in cases vs controls. The assessment will be through serum analysis. We will be assessing 71 cytokines using Human Cytokine Array/Chemokine Array: sCD40L, EGF, Eotaxin, FGF-2, Flt-3 ligand, Fractalkine, G-CSF, GM-CSF, GROa, IFNa2, IFN?, IL-1a, IL-1ß, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17E/IL-25, IL-17F, IL-18, IL-22, IL-27, IP-10, MCP-1, MCP-3, M-CSF, MDC (CCL22), MIG, MIP-1a, MIP-1ß, PDGF-AA, PDGF-AB/BB, RANTES, TGFa, TNFa, TNFß, VEGF-A, 6Ckine, BCA-1, CTACK, ENA-78, Eotaxin-2, Eotaxin-3, I-309, IL-16, IL-20, IL-21, IL-23, IL-28A, IL-33, LIF, MCP-2, MCP-4, MIP-1d, SCF, SDF-1A+ß, TARC, TPO, TRAIL, TSLP. This is an exploratory outcome measure.
Timepoint [1] 324811 0
There are two timepoints, enrolment in the study, then a second sample within 1 year during a period when the person expresses a subjective feeling of being unwell. Healthy participants samples will be taken after a minimum of 1 month following their first sample but no longer than 12 months. All blood samples will be collected fasting between 8am and 10am.
Secondary outcome [1] 387735 0
Sleep quality measured using a sleep monitor. This is to assess both the quality of sleep and depth of sleep. The device will collect movement and breathing rate. This is part of the symptom information and will be used will tested for correlation with cytokines and for the difference between cases and controls.
Timepoint [1] 387735 0
At baseline i.e. A timepoint 1 within one week of initial blood samples.
Secondary outcome [2] 387935 0
Relationship of BMI will tested for correlation with cytokines and for the difference between cases and controls. This will be measured using balance scales for weight, and height using a stadiometer.
Timepoint [2] 387935 0
Baseline- timepoint 1
Secondary outcome [3] 387936 0
blood glucose levels will tested for correlation with cytokines and for the difference between cases and controls..
Timepoint [3] 387936 0
Baseline - timepoint 1
Secondary outcome [4] 387937 0
Depression symptoms - assessing depression symptoms across the cohort and these will tested for correlation with cytokines and for the difference between cases and controls. This will be assessed with the Hamilton Depression Scale (HAMD).
Timepoint [4] 387937 0
Timepoint 1
Secondary outcome [5] 387938 0
Physical activity will be assessed using the Global Physical Activity Questionnaire (GPAQ) and will be used to analyse the relationship of symptoms and cytokine outcomes, which will also be used to compare differences in cases and controls. We will also have a voluntary app which will be used to collect activity data. This will be used for at least one week at timepoint 1 then the participant can continue to use it to monitor activity for as long as preferred, or at a frequency preferred. Up to the second timepoint.
Timepoint [5] 387938 0
Timepoint 1
Secondary outcome [6] 387939 0
Diet and eating behaviour will be assessed using a diary, which will include times of meals and an approximation of food portions and food type. This will be assessed in the week following the initial blood sample at timepoint 1.
Timepoint [6] 387939 0
timepoint 1
Secondary outcome [7] 387940 0
A list of current medications and supplements will be collected to assess any relationship with the cytokine outcomes. This will be a self report at timepoint 1. A simple list of self reported current medications, and supplements.
Timepoint [7] 387940 0
Timepoint 1
Secondary outcome [8] 387991 0
Symptoms of MECFS will be collected as part of the baseline assessment using the DePaul Symptom Questionnaire (DSQ-2).
Timepoint [8] 387991 0
Timepoint 1
Secondary outcome [9] 387992 0
Waist to Hip ratio will be measured by the clinician on the day of blood draw - at timepoint 1.
Timepoint [9] 387992 0
Timepoint 1
Secondary outcome [10] 387993 0
This is a composite set of symptoms that will be collected as part of the symptom monitoring of MECFS. The symptoms are listed below and will be collected on a simple scale of 0 (no symptoms) to 10 severe symptoms. The list is taken from the Canadian Consensus Criterion:
: Fatigue: persistent, marked fatigue that substantially reduces activity level; Sleep Disturbance: non-restorative sleep, insomnia, hypersomnia; Pain: in muscles, joints, headaches; Memory disturbance: poor short term memory; Confusion and difficulty concentrating; Difficulty retrieving words or saying the wrong word; Gastrointestinal disturbance: diarrhea, IBS; Recurrent sore throat; Recurrent flu-like symptoms; Dizziness or weakness upon standing; Change in body temperature, erratic body temperature, cold hand and feet; Heat / cold intolerance; Hot flushes, sweating episodes; Marked weight change; Breathless with exertion; Tender lymph nodes: especially at sides of neck and under arms; Sensitive to light, noise, or odours; Muscle weakness; New sensitivities to food / medications /chemicals.We will also have a voluntary app which will be used to collect symptom data. This will be used for at least one week at timepoint 1 then the participant can continue to use it to monitor activity for as long as preferred, or at a frequency preferred. Up to the second timepoint.
Timepoint [10] 387993 0
Timepoint 1 - it is a voluntary aspect of the research and can be used by the participant up until timepoint 2. Initial assessment will be used at timepoint 1 for 1 week.

Eligibility
Key inclusion criteria
Participants will have a diagnosis of ME/CFS. They will be based in South Australia unless special arrangements can be organised to collect bloods interstate. A formal diagnosis of ME/CFS will have been made by a general practitioner or medical specialist. They will also consent for their GP to be provided with information if required for example feedback about clinical levels of moderate to severe depression. Healthy participants will be those who do not have other current physical health or mental health problems. They will also consent for their GP to be provided with information if required for example feedback about clinical levels of moderate to severe depression.

Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criterion includes hormonal disorders, major physical or mental health disorders, or outside of the age range. Exclusion criteria include pregnancy, other diseases requiring medication that may affect the results, alcohol or substance abuse or dependence. Other physical disorders that may confound the measurements listed earlier, such as anaemia, or a thyroid disorder. Any mental health disorder that requires medication, psychosis, affective disorders. Low dosages of antidepressant for the purpose of sleep will be accepted. Being unable to understand the consent process due to language or an inability to read English. Must be at least 18 years of age, and up to 65 years.
Morbid Obesity will be an exclusion factor i.e. must have a BMI <40 (35 equates to the WHO obesity type ii and 40 morbidly obese).

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Case control
Timing
Prospective
Statistical methods / analysis
Simple comparison between 2 time points, then compared with controls

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/11/2020
Actual
Date of last participant enrolment
Anticipated
1/03/2022
Actual
Date of last data collection
Anticipated
30/03/2023
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 17275 0
South Australian Health and Medical Research Institute (SAHMRI) - Adelaide
Recruitment postcode(s) [1] 30988 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 306487 0
Charities/Societies/Foundations
Name [1] 306487 0
The Judith Jane Mason & Harold Stannett Williams Memorial Foundation National Medical Program (Alzheimer's disease & Chronic Fatigue Syndrome)
Country [1] 306487 0
Australia
Primary sponsor type
Other
Name
South Australian Health & Medical Research Institute
Address
North Terrace, Adelaide, South Australia, SA 5000
Country
Australia
Secondary sponsor category [1] 307009 0
None
Name [1] 307009 0
Address [1] 307009 0
Country [1] 307009 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306692 0
University of Adelaide HREC
Ethics committee address [1] 306692 0
University of Adelaide
HREC
LEVEL 4, RUNDLE MALL PLAZA
50 RUNDLE MALL
ADELAIDE SA 5000 AUSTRALIA
Ethics committee country [1] 306692 0
Australia
Date submitted for ethics approval [1] 306692 0
12/11/2019
Approval date [1] 306692 0
27/07/2020
Ethics approval number [1] 306692 0
H-2020-134

Summary
Brief summary
The aim of the project is to examine the underlying biology of 40 people who have been diagnosed with ME/CFS (Myalgic encephalomyelitis / Chronic Fatigue Syndrome) by their general practitioner comparing these symptoms to people who are well (controls) . We have brought together a team of clinicians and researchers to investigate ME/CFS from a multidisciplinary perspective. The diagnosis will be confirmed using the Canadian Consensus ME/CFS definition, interviews and questionnaires. We will aim to take blood samples, urine and faecal samples at times when the sufferer is experiencing what is often referred to as a ‘crash’ (a period of significant worsening of symptoms and accompanying greater impairment). Another set of samples will be taken when the person is feeling relatively well. A series of questionnaires will be used to obtain information about symptoms and experiences. We will examine the differences in the blood, urine and faecal samples across these two times. Samples will be taken as early as possible to allow for fasting i.e. between 8am and 10am to be negotiated with participant. There are no interventions or medications involved in this research. The most invasive aspects of the research is 2 sets of blood samples (51mls occasion 1 and 36mls occasion 2) and some questionnaires. This is an observational study.
Trial website
Trial related presentations / publications
Public notes
Please contact us to discuss your potential involvement in this project: email [email protected]

Contacts
Principal investigator
Name 104690 0
Dr Michael Musker
Address 104690 0
SAHMRI
North Terrace,
South Australia
SA 5000
Country 104690 0
Australia
Phone 104690 0
+61 08 8128 4714
Fax 104690 0
Email 104690 0
[email protected]
Contact person for public queries
Name 104691 0
Dr Michael Musker
Address 104691 0
SAHMRI
North Terrace,
South Australia
SA 5000
Country 104691 0
Australia
Phone 104691 0
+61 08 8128 4714
Fax 104691 0
Email 104691 0
[email protected]
Contact person for scientific queries
Name 104692 0
Dr Michael Musker
Address 104692 0
SAHMRI
North Terrace,
South Australia
SA 5000
Country 104692 0
Australia
Phone 104692 0
+61 08 8128 4714
Fax 104692 0
Email 104692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The deidentified cytokine results, demographics
When will data be available (start and end dates)?
At the end of the study and for 10 years following publication
Available to whom?
Other researchers researchers who provide a methodologically sound proposal, and as part of the publication process.
Available for what types of analyses?
As per statement above and for the aims in the approved proposal, and for IPD meta-analyses upon request and where a research link can be identified in relation to MECFS.
How or where can data be obtained?
From the lead researcher following approval: [email protected]


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.