Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001316594
Ethics application status
Approved
Date submitted
3/10/2024
Date registered
30/10/2024
Date last updated
30/10/2024
Date data sharing statement initially provided
30/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
An imaging-based approach to investigate the pathophysiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Long COVID and Postural Orthostatic Tachycardia Syndrome
Scientific title
An imaging-based approach to investigate the pathophysiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Long COVID and Postural Orthostatic Tachycardia Syndrome in females aged 18 - 70 years old
Secondary ID [1] 312957 0
None
Universal Trial Number (UTN)
Trial acronym
MELOPIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome 335275 0
Long COVID 335276 0
Postural Orthostatic Tachycardia Syndrome 335277 0
Condition category
Condition code
Other 331848 331848 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)
Respiratory 331852 331852 0 0
Other respiratory disorders / diseases
Cardiovascular 331853 331853 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Online questionnaires: All participants(ME/CFS, Long COVID, POTS patient group and healthy control group) will be sent a web link to a series of online questionnaires to be completed prior to clinic visits. REDCap is a secure web platform for building and managing online databases and surveys. There are seven questionnaires which will take about three hours in total..

Clinic visits: All participants(ME/CFS, Long COVID, POTS patient group and healthy control group) will be asked to visit the Melbourne Brain Centre Imaging Unit (MBCIU) twice. The first visit will take approx. 2 hours, the second approx. 4 hours. The two visits should be separated more than 2 days. An investigator will accompany participants through these two visits. In addition, an registered nurse will assess participants' status by direct observation and equipment inspection. The medical procedures for these two visits are summarised as follows.

Blood collection(both visit1 and visit2):10 mL of fasting whole blood will be collected by trained staff at visit1.
10 mL of whole blood will be collected prior and after to the MRI by trained staff at visit2.

Random Blood Glucose Test(visit1): Participants will be asked to prick their finger to provide a small sample of blood, which will then be analysed using a blood glucose meter.

Urine collection and pregnancy test(both visit1 and visit2):At each clinic visit, a 20ml sample of midstream urine will be collected by participants themselves. After collecting the urine, it is applied by the clinic nurse to a test strip or cassette, which will indicate the result of pregnancy within a few minutes.

10 minutes standing test:(visit1) At visit1, participants will be asked to remove their shoes and lie on their back. After lying quietly for 5-10 minutes, their blood pressure and pulse will be recorded. Next, participants will be asked to rise and stand straight while leaning against the wall for 10 minutes. Their blood pressure and pulse measurements will be recorded every minute from the Caretaker Vital Stream which is a wireless, wearable continuous cardiac output, and blood pressure monitor.

18F-Fluorodeoxyglucose(FDG) PET Scan(visit1): At visit1, participants will get a small amount of 18F-FDG, injected into a vein in their arm. After the injection, they will stand for 10 minutes and then rest in a quiet, dark room for 20 minutes. Next, they will have a 30-minute brain scan, followed by a 15-minute scan of their lower legs. After the scan, they will be checked if they feel okay before they go home.

Brain MRI and MRS scan(visit2): Prior to the MRI session, participants will receive an email to familiarise themselves with the scanning procedure and be asked to fill out an safety screening form. At visit2, both MRI and MRS scan will be undertaken lying down in an scanner for about 60 minutes in total. Whilst lying in the scanner, they will be able to watch a video of their choosing. For brief periods they will be asked to respond to some prompts on the screen by squeezing a force measuring device.

18F-SMBT-1 PET Scan(visit2): At visit2, participants will receive an injection of the tracer 18F-SMBT-1 into a vein in their arm. After allowing one hour for the tracer to circulate around the body, they will have a 30-minute brain scan. This will be followed by a 15-minute scan of lower legs. After the scan, they will be checked to ensure they’re feeling well before they go home.
Intervention code [1] 329605 0
Diagnosis / Prognosis
Comparator / control treatment
We plan to compare ME/CFS group with healthy control group, LONG Covid group with healthy control group, compare between ME/CFS with POTS and without POTS, compare between LONG Covid with POTS and without POTS.

All groups will use the same interventions, questionnaires and clinic visits.
Control group
Active

Outcomes
Primary outcome [1] 339470 0
Neuroinflammation level in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome(ME/CFS), Long COVID patients compared to the control group
Timepoint [1] 339470 0
Clinic visit day1 and Clinic visit day2
Primary outcome [2] 339546 0
Brain metabolites(glutamate) will be assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [2] 339546 0
Clinic visit day2
Primary outcome [3] 339547 0
Cerebral blood flow at rest and both during and after physical activity between patients(ME/CFS and Long COVID) and control groups
Timepoint [3] 339547 0
Clinic Visit Day2
Secondary outcome [1] 440112 0
Serum cortisol levels in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [1] 440112 0
Clinic Visit Day1 and Day2
Secondary outcome [2] 440627 0
Fatigue will be comprehensively assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [2] 440627 0
Before the first Clinic Visit
Secondary outcome [3] 440885 0
Serum growth hormone level in patients(ME/CFS and and Long COVID) compared to control group
Timepoint [3] 440885 0
Clinic visit Day1 and Day2
Secondary outcome [4] 440886 0
Serum thyroid hormone in patients(ME/CFS and Long COVID) compared to control group
Timepoint [4] 440886 0
Clinic visit Day1 and Day2
Secondary outcome [5] 441062 0
Brain metabolites(GABA) will be assessed in patients (ME/CFS and Long COVID) compared to the control group-primary outcome
Timepoint [5] 441062 0
Clinic Visit day2
Secondary outcome [6] 441063 0
Brain metabolites(lactate) will be assessed in patients (ME/CFS and Long COVID) compared to the control group-primary outcome
Timepoint [6] 441063 0
Clinic Visit day2
Secondary outcome [7] 441064 0
Post Exertional Malaise will be assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [7] 441064 0
Before first clinic visit
Secondary outcome [8] 441065 0
Pain will be comprehensively assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [8] 441065 0
Before first clinic visit
Secondary outcome [9] 441066 0
Autonomic nervous system symptoms will be assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [9] 441066 0
Before first clinic visit
Secondary outcome [10] 441068 0
Reproductive system symptoms will be assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [10] 441068 0
Before first clinic visit
Secondary outcome [11] 441150 0
Postural orthostatic tachycardia syndromes (POTS) will be assessed in patients (ME/CFS and Long COVID) compared to the control group
Timepoint [11] 441150 0
Before the first clinic visit

Eligibility
Key inclusion criteria
This project is investigating ME/CFS and Long COVID with or without POTS in female adults that are age between 18-70 years old. Patients previously diagnosed with ME/CFS and/or Long COVID and age-matched health controls will be invited to screen for the MELOPIS Study.
A research doctor will meet candidates in person or virtually (via telehealth call or video link) and confirm their eligibility based on whether candidates meet diagnostic standards recommended by professional research organisations (Canadian Consensus Criteria or the National Institute for Health and Care Excellent guidelines for ME/CFS or the World Health Organization condition of Long COVID) .

Healthy controls need meet below inclusion criteria and will be confirmed their eligibility be research doctor.
1. 18-70 years female
2. Fluent in English
3. Self-identifies as healthy
4. Covered by Medicare or an equivalent from health care insurance.
Minimum age
18 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All patients and health controls should exclude the following conditions.
1. Pregnancy or those currently attempting to become pregnant
2. Pre-existing renal disease (>CKD3b)
3. Severe chronic respiratory disease
4. Diabetes (any sort).
5. Cardiac disease, including valvulopathy of moderate grade or higher, any ischemic heart disease, arrhythmias other than sinus atrial node disease without syncope.
6. BMI <17, >40
7. Uncontrolled hypertension.
8. Active or treated cancer within the last 5 years.
9. Immunosuppressive treatments (prednisolone >7.5mg/day) or conditions. 10. Significant degenerative arthritis
11. Multiple Sclerosis.
12. Severe needle aversion.
13. Significant intellectual disabilities.
14. Breastfeeding.
15. Psychiatric disorders.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
For the case-control comparisons, we will have data for all tests for 26 ME/CFS patients, 26 Long COVID patients and 26 healthy controls; this cohort was based on a power calculation of 0.95, a difference between means of 10%, and a type-1 error rate of 5%. We would expect a power above 0.9 if only 22 subjects from each cohort complete the study (15% attrition rate).

LCModel will be used to analyze the spectra from MRS scan and obtain the absolute value and the value relative to myo-inositol of different metabolites in hypothalamus region. ELISA Kits will be used to obtain the serum hormones level. In addition, we quantify the survey and obtain standardized values. After that, the Welch t-test and the nonparametric Mann-Whitney U test will be used to compare cases and controls while we will also look for univariate associations between key variables using correlation co-efficients. All statistical analysis will be conducted using Excel, SPSS and R.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
1/10/2026
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
78
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317388 0
Charities/Societies/Foundations
Name [1] 317388 0
open medicine foundation
Country [1] 317388 0
Australia
Primary sponsor type
University
Name
The university of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 319786 0
None
Name [1] 319786 0
None
Address [1] 319786 0
Country [1] 319786 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316116 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316116 0
Ethics committee country [1] 316116 0
Australia
Date submitted for ethics approval [1] 316116 0
06/06/2024
Approval date [1] 316116 0
12/09/2024
Ethics approval number [1] 316116 0
2024-29235-57752-5

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136842 0
Dr Christopher Armstrong
Address 136842 0
Bio21 institute, 30 flemington road, Parkville, 3052, Victoria
Country 136842 0
Australia
Phone 136842 0
+61 421500027
Fax 136842 0
Email 136842 0
[email protected]
Contact person for public queries
Name 136843 0
Ellen Wang
Address 136843 0
Bio21 institute, 30 flemington road, Parkville, 3052, Victoria
Country 136843 0
Australia
Phone 136843 0
+61 0431687548
Fax 136843 0
Email 136843 0
[email protected]
Contact person for scientific queries
Name 136844 0
Ellen Wang
Address 136844 0
Bio21 institute, 30 flemington road, Parkville, 3052, Victoria
Country 136844 0
Australia
Phone 136844 0
+61 0431687548
Fax 136844 0
Email 136844 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
to protect each participant's privacy


What supporting documents are/will be available?

No Supporting Document Provided



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.