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Trial registered on ANZCTR


Registration number
ACTRN12621000597897
Ethics application status
Approved
Date submitted
6/04/2021
Date registered
19/05/2021
Date last updated
6/03/2023
Date data sharing statement initially provided
19/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Changes to the immune system after vitamin D supplementation in healthy individuals and people with multiple sclerosis
Scientific title
Effect of vitamin D supplementation on immune cells of healthy adults and adults with multiple sclerosis
Secondary ID [1] 303864 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple sclerosis 321435 0
Condition category
Condition code
Neurological 319196 319196 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vitamin D3 10,000 IU oral tablet daily for 4 weeks.
At week 4 follow-up visit, participant's compliance will be assessed by participant self-report and by pill count.
Intervention code [1] 320171 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327065 0
Change in gene expression of immune cell subsets. Gene expression will be assessed by RNA-sequencing of immune cell subsets isolated from collected peripheral blood samples.
Timepoint [1] 327065 0
Baseline, 4 weeks
Primary outcome [2] 327066 0
Change in peripheral immune cell phenotype, assessed by flow cytometry of blood samples.
Timepoint [2] 327066 0
Baseline, 4 weeks
Secondary outcome [1] 393664 0
Nil
Timepoint [1] 393664 0
Nil

Eligibility
Key inclusion criteria
• Aged between 18 and 65 years old inclusive
• No Vitamin D supplementation for at least 1 month prior
• Be willing to avoid open-label Vitamin D supplementation and external serum Vitamin D testing for the duration of the study
• Be willing to avoid the use of sunbeds
• Not currently pregnant or planning to become pregnant during the study period, and willing to use effective contraceptive methods for the duration of the study
• Be able and willing to comply with all study procedures
• Be able to give informed consent and sign the informed consent form

Additional inclusion criteria for healthy participants are:
• No diagnosis of MS or CIS, or significant chronic disease

Additional inclusion criteria for participants with MS are:
• Relapsing-remitting MS diagnosed within the previous 10 years, meeting McDonald criteria for the diagnosis of MS
• Either on no DMT or on natalizumab prior to and during the study period
• Diagnosed and managed by a neurologist
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Currently pregnant or breastfeeding
• A history of primary hyperparathyroidism or any other condition causing hypercalcaemia
• A history of sarcoidosis
• A history of renal calculi
• A history of treated osteoporosis or any other condition requiring treatment with calcium, Vitamin D, bisphosphonates, strontium ranelate, denosumab, raloxifene, calcitriol or teriparetide
• Hypercalcaemia, abnormal eGFR (<60 mL/min/1.73m2) or an elevated uric acid laboratory value on screening blood tests
• Other neurological, psychiatric or other disease comorbidities which, in the opinion of the investigator, could impair capacity to provide informed consent, interfere with study compliance, or impair the participant’s ability to comply with study protocol
• Current enrolment in another drug interventional trial

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
Statistical methods / analysis
We used human monocyte gene expression data derived from a previous genomic study (Risk Gene) to perform power calculations using the R package pwr. We calculated that with a sample size of 12, we would have at least 80% power at a significance level of 0.05 to detect an at least 20% change in gene expression based on paired t-tests for the following genes: CD14, ZMIZ1, IRF8, CLMN, FBP1. These genes have been identified as vitamin D-responsive genes in in vitro studies of monocytic cell lines or human blood-derived monocytes and dendritic cells (Neme et al., 2017; Parnell et al., 2019). Differential gene expression analyses will be conducted using publicly available software and analyses pipelines. Functional clustering and pathway analyses will be conducted using publicly available databases to investigate processes or pathways regulated by Vitamin D.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Decided not to continue based on recently presented findings from PrevANZ study (negative for primary endpoint), as well as recently published microarray transcriptomic study of changes in immune cell subsets from MS patients after high dose vitamin D (modest changes).
Date of first participant enrolment
Anticipated
17/01/2022
Actual
10/02/2022
Date of last participant enrolment
Anticipated
Actual
8/07/2022
Date of last data collection
Anticipated
Actual
8/07/2022
Sample size
Target
72
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 19063 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 33613 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 308260 0
University
Name [1] 308260 0
Monash University
Country [1] 308260 0
Australia
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
55 Commercial Road, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 309051 0
None
Name [1] 309051 0
Address [1] 309051 0
Country [1] 309051 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308238 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 308238 0
Ethics committee country [1] 308238 0
Australia
Date submitted for ethics approval [1] 308238 0
07/04/2021
Approval date [1] 308238 0
23/07/2021
Ethics approval number [1] 308238 0

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

Contacts
Principal investigator
Name 110026 0
Prof Helmut Butzkueven
Address 110026 0
MS and NeuroImmunology Unit, Level 6, Alfred Centre, The Alfred Hospital, 99 Commercial Road, Melbourne VIC 3004 Australia
Country 110026 0
Australia
Phone 110026 0
+61 3 99038662
Fax 110026 0
Email 110026 0
helmut.butzkueven@monash.edu
Contact person for public queries
Name 110027 0
Wei Yeh
Address 110027 0
MS and NeuroImmunology Unit, Level 6, Alfred Centre, The Alfred Hospital, 99 Commercial Road, Melbourne VIC 3004 Australia
Country 110027 0
Australia
Phone 110027 0
+61 3 99038662
Fax 110027 0
Email 110027 0
wei.yeh@monash.edu
Contact person for scientific queries
Name 110028 0
Wei Yeh
Address 110028 0
MS and NeuroImmunology Unit, Level 6, Alfred Centre, The Alfred Hospital, 99 Commercial Road, Melbourne VIC 3004 Australia
Country 110028 0
Australia
Phone 110028 0
+61 3 99038662
Fax 110028 0
Email 110028 0
wei.yeh@monash.edu

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.