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Trial registered on ANZCTR


Registration number
ACTRN12624000423516
Ethics application status
Approved
Date submitted
14/03/2024
Date registered
8/04/2024
Date last updated
8/04/2024
Date data sharing statement initially provided
8/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Reducing Fatigue In Relapsing Multiple Sclerosis: An Epstein Barr Virus Treatment Trial (FIRMS EBV)
Scientific title
Fatigue In Relapsing Multiple Sclerosis Epstein Barr Virus Treatment Trial (FIRMS EBV) - Comparing Spironolactone, Tenofovir Alafenamide and Placebo
Secondary ID [1] 311741 0
None
Universal Trial Number (UTN)
Trial acronym
FIRMS EBV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 333223 0
Epstein Barr Virus 333425 0
Condition category
Condition code
Neurological 329913 329913 0 0
Multiple sclerosis
Infection 330101 330101 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - Spironolactone
25mg oral capsule twice daily for first week, then 50mg oral capsule twice daily for next 15 weeks.

Arm 2 - Tenofovir Alafenamide (TAF)
25mg oral capsule daily for 16 weeks.

Both interventions will be administered as an add-on to participants' usual MS treatments (disease-modifying therapies (DMT)) and they will continue taking these as prescribed by their treating doctor.

Participants will return all unused study drug including empty bottles at study visits so that compliance can be checked.
Intervention code [1] 328197 0
Treatment: Drugs
Comparator / control treatment
Arm 3 - Placebo
Placebo capsule consisting of microcrystalline cellulose, lactose monohydrate, magnesium stearate and croscarmellose sodium, to be taken twice daily for 16 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 337678 0
Fatigue
Timepoint [1] 337678 0
Baseline and after 16 weeks of treatment
Secondary outcome [1] 432811 0
Fatigue
Timepoint [1] 432811 0
Baseline and after 16 weeks of treatment

Eligibility
Key inclusion criteria
1. Male and female participants aged 18-65 years
2. Diagnosed with relapsing remitting Multiple Sclerosis (MS) by a neurologist
3. Expanded Disability Status Scale (EDSS) score of 6 within the last 12 months in the absence of an acute relapse or illness
4. Stable and have not received a new MS therapy in the preceding 8 weeks
5. Willingness to provide informed consent and willingness to participate and comply with the study requirements
6. Available to attend clinic visits within 1 week of each time point (baseline, Weeks 6, 16, and 20)
7. Clinical fatigue (evidenced by an FSS score greater than 4 on two occasions when completing the test serially online or in person over a fortnight)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants treated with the MS disease-modifying therapy, cladribine (since TAF interacts with this drug) or the mood stabilizing agent, lithium (which interacts with spironolactone)
2. Treatment with angiotensin converting enzyme inhibitors or angiotensin 2 receptor blockers
3. A systemic medical disorder such as kidney disease or new diagnosis of hyper- or hypothyroidism OR any medical condition that may affect adherence to the trial intervention
4. Psychotropic medications if commenced < 4 weeks prior to study entry
5. Currently pregnant or lactating or if of child bearing potential, unwilling to take adequate contraception measures to prevent pregnancy for the duration of the clinical trial and for 2 weeks after trial completion
6. Commenced or are scheduled to commence iron supplementation
7. Acute suicidality (as per the Quick Inventory of Depressive Symptomology Tool) or a current diagnosis of substance abuse/dependence
8. Currently taking any illicit substances including any cannabis product (e.g. cannabis oil)
9. Recent gastrointestinal ulcers or renal stones
10. Epilepsy
11. Current use of any of the study drugs
12. Unable or unlikely to attend the required study visits at the required timepoints or unable to complete the study protocol
13. Lacks the capacity to consent as determined by the treating clinician

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Yes - allocation concealed by central randomisation via the study statistician, whom is off-site and will be contacted for the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation and minimisation, Factors considered will be age, level of disability, treatment (no/low efficacy versus high efficacy disease modifying therapy) and recruiting site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample of 80 subjects per arm has 90% power to detect a minimum median difference of 0.81 of a FSS point from a pre-intervention baseline of FSS=543 and a minimum difference of 13.6 points on the MFIS scale from a pre-intervention baseline of MFIS=509, both at the 5% significance level. A 10% loss to follow-up or sample attrition is anticipated. These calculations are based on a previous study which showed that the minimum change in fatigue scores in those with MS that is clinically meaningful is 0.45 points for the FSS and 4 points for the MFIS.

For all outcomes, an intention to treat analysis will be conducted by the study statistician who will not be blinded to the treatment allocations. The continuous primary and secondary outcome data will be analysed using mixed model, hierarchical linear modelling, nested within treatment groups, taking time as a within-subjects effect and grouped as a between-subject effect. This includes adjusting for non-MS related factors that may cause fatigue such as sleep quality and exercise.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2027
Actual
Date of last data collection
Anticipated
31/05/2028
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,WA,VIC
Recruitment hospital [1] 26267 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 26268 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [3] 26269 0
The Alfred - Melbourne
Recruitment hospital [4] 26270 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 26271 0
John Hunter Hospital - New Lambton
Recruitment hospital [6] 26272 0
Launceston General Hospital - Launceston
Recruitment hospital [7] 26273 0
Gold Coast University Hospital - Southport
Recruitment hospital [8] 26274 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [9] 26278 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [10] 26279 0
Liverpool Hospital - Liverpool
Recruitment hospital [11] 26280 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment hospital [12] 26281 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 42238 0
2139 - Concord
Recruitment postcode(s) [2] 42239 0
2050 - Camperdown
Recruitment postcode(s) [3] 42240 0
3004 - Melbourne
Recruitment postcode(s) [4] 42241 0
2065 - St Leonards
Recruitment postcode(s) [5] 42242 0
2305 - New Lambton
Recruitment postcode(s) [6] 42243 0
7250 - Launceston
Recruitment postcode(s) [7] 42244 0
4215 - Southport
Recruitment postcode(s) [8] 42245 0
4029 - Herston
Recruitment postcode(s) [9] 42249 0
3050 - Parkville
Recruitment postcode(s) [10] 42250 0
2170 - Liverpool
Recruitment postcode(s) [11] 42251 0
6009 - Nedlands
Recruitment postcode(s) [12] 42252 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 316073 0
Government body
Name [1] 316073 0
National Health and Medical Research Council
Country [1] 316073 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 318240 0
None
Name [1] 318240 0
Address [1] 318240 0
Country [1] 318240 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314892 0
Sydney Local Health District HREC – Concord Repatriation General Hospital
Ethics committee address [1] 314892 0
http://www.slhd.nsw.gov.au/concord/ethics/
Ethics committee country [1] 314892 0
Australia
Date submitted for ethics approval [1] 314892 0
06/12/2023
Approval date [1] 314892 0
21/02/2024
Ethics approval number [1] 314892 0
2023/ETH01992

Summary
Brief summary
Existing Multiple Sclerosis (MS) therapies are effective at reducing MS relapses but there is currently no effective therapy for treating MS related fatigue. There is an understanding that chronic Epstein Barr Virus (EBV) infection of immune cells, called B lymphocytes, might be a driver of chronic symptoms in MS, such as fatigue. As such, this trial examines whether treating EBV infection can improve MS-related fatigue. The study tests two 'repurposed' anti-viral drugs, 'Tenofovir alafenamide' and 'Spironolactone', as an add-on to standard MS treatment for 16 weeks to see if fatigue can improve in participants with relapsing MS. We hypothesise that both Tenofovir alafenamide and Spironolactone will improve measures of fatigue in participants with relapsing MS compared to placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133070 0
A/Prof Todd Hardy
Address 133070 0
Department of Neurology, Concord Hospital, Hospital Rd, Concord West NSW 2139
Country 133070 0
Australia
Phone 133070 0
+61 2 9767 6416
Fax 133070 0
Email 133070 0
[email protected]
Contact person for public queries
Name 133071 0
Shani Lauf
Address 133071 0
Department of Neurology, Concord Hospital, Hospital Rd, Concord West NSW 2139
Country 133071 0
Australia
Phone 133071 0
+61 2 9767 7259
Fax 133071 0
Email 133071 0
[email protected]
Contact person for scientific queries
Name 133072 0
A/Prof Todd Hardy
Address 133072 0
Department of Neurology, Concord Hospital, Hospital Rd, Concord West NSW 2139
Country 133072 0
Australia
Phone 133072 0
+61 2 9767 6416
Fax 133072 0
Email 133072 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


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.