Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001160820
Ethics application status
Approved
Date submitted
30/10/2012
Date registered
1/11/2012
Date last updated
13/12/2021
Date data sharing statement initially provided
8/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Preventing the risk of Multiple Sclerosis using Vitamin D in patients with a first demyelinating event in Australia and New Zealand (PrevANZ)
Scientific title
Phase IIb Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Trial to determine the safety and efficacy of Vitamin D3 in preventing the risk of MS in Patients with a first demyelinating event.
Secondary ID [1] 281218 0
Nil
Universal Trial Number (UTN)
U1111-1134-6119
Trial acronym
PrevANZ
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clinically Isolated Syndrome - those who have experienced only one demyelinating event and are yet to receive a diagnosis of clinically definite Multiple Sclerosis (MS). 287408 0
Condition category
Condition code
Neurological 287741 287741 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vitamin D 1,000IU; 5,000IU; 10,000IU.
Arm 1: Placebo once daily oral capsule for 48 weeks;
Arm 2: Vitamin D 1,000IU once daily oral capsule for 48 weeks;
Arm 3: Vitamin D 5,000IU once daily oral capsule for 48 weeks and
Arm 4: Vitamin D 10,000IU once daily oral capsule for 48 weeks.
Intervention code [1] 285687 0
Prevention
Comparator / control treatment
Placebo once daily oral capsule for 48 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 287975 0
To determine the relative efficacy of oral, daily, Vitamin D3 (1,000IU or 5000IU or 10,000IU) compared with placebo, in reducing the risk of recurrent disease activity (clinical demyelinating event or MRI activity) in the 12 months following onset of a first demyelinating event.
Timepoint [1] 287975 0
12 months following onset of a first demyelinating event.
Secondary outcome [1] 299168 0
To assess whether a beneficial clinical and/or radiological response exists for oral Vitamin D supplementation in preventing MS in high-risk FDE participants
Timepoint [1] 299168 0
12 months post randomisation
Secondary outcome [2] 299169 0
To assess whether there is a dose response relationship between study medication and the study endpoints
Timepoint [2] 299169 0
12 months post registration
Secondary outcome [3] 299170 0
To assess whether there is a relationship between serum 25(OH)D level and study endpoints
Timepoint [3] 299170 0
12 months post randomization
Secondary outcome [4] 299171 0
To determine if oral Vitamin D3 therapy has an acceptable side effect and safety profile by monitoring the adverse events over the 12 months. Blood calcium will be monitored at each timepoint because there is the unlikely possibility that it may increase.
Timepoint [4] 299171 0
12 months post randomisation

Eligibility
Key inclusion criteria
For inclusion in this study, a participant must meet the following criteria:
* aged between 18 and 65 years old inclusive
* have a first isolated, well-defined, uni- or multi-focal first demyelinating event (FDE)
* be able to receive first dose of study drug within 135 days of FDE symptom onset
* have an MRI brain scan that is supportive of demyelinating disease (Paty A or Paty B criteria) OR have at least one >5mm diameter T2/Flair brain lesion which must be in a periventricular, callosal, subcortical U-fibre or posterior fossa location AND must have at least one spinal cord lesion.
* an EDSS between 0 - 6.5 (inclusive)
* be able to give informed consent and sign the informed consent form
* 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 use of sunbeds
* not have received any prior disease modifying treatment for MS other than glucocorticoids
* be willing to avoid treatment with beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, or other chemotherapy agent specifically for demyelinating disease until recurrent disease activity occurs (ie the primary endpoint is met)
* be able and willing to comply with all study procedures including MRI scanning as per protocol
* be willing to use effective contraceptive methods for the duration of the study and at least 6 months following.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any of the following conditions will exclude a participant from the study:
* currently pregnant or breastfeeding
* documented or likely prior neurological event consistent with a diagnosis of clinically definite MS
* treatment with beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, or other chemotherapy agent specifically for demyelinating disease
* a second clinical demyelinating event prior to randomisation
* 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, bisposphonates, strontium ranelate, denosumab, raloxifene, calcitriol or teriparetide
* hypercalcaemia on screening blood tests
* an abnormal eGFR (<60 ml/min/1.73m2), or an elevated uric acid laboratory value (above normal range for the local laboratory used)
* concurrent diagnosis of other neurological, psychiatric or other disease 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 the study protocol
* current enrolment in another interventional trial
* any contraindication to MRI scanning or intravenous Gadolinium including:
a) cardiac pacemaker
b) cardiac defibrillator
c) metal fragments in the eye
d) any other non-MRI compatible medical device/implant or medical condition
e) previous reaction to Gadolinium
f) severe claustrophobia.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants presenting to the Neurology Department will be assessed to determine their eligibility.

If the participant gives informed consent, they will be randomized to either placebo or 3 arms of active drug.

Allocation to treatment will be concealed by numbered bottles allocated to sites using central computerised allocation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be based on simple randomization created by computer software to promote balanced randomization with equal numbers in each arm, stratified by site/centre.
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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/12/2012
Actual
8/07/2013
Date of last participant enrolment
Anticipated
31/12/2019
Actual
3/01/2020
Date of last data collection
Anticipated
31/12/2020
Actual
4/12/2020
Sample size
Target
240
Accrual to date
Final
202
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 4315 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 4316 0
Royal Hobart Hospital - Hobart
Recruitment hospital [3] 4317 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 4318 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [5] 4319 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [6] 4320 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [7] 4324 0
The Wesley Hospital - Auchenflower
Recruitment hospital [8] 7259 0
Calvary Wakefield Hospital - Adelaide
Recruitment hospital [9] 7260 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [10] 7261 0
The Western Australian Neuroscience Research Institute - Nedlands
Recruitment hospital [11] 7262 0
Gold Coast University Hospital - Southport
Recruitment hospital [12] 13974 0
The Alfred - Prahran
Recruitment postcode(s) [1] 5906 0
3050
Recruitment postcode(s) [2] 5907 0
7000
Recruitment postcode(s) [3] 5912 0
3168
Recruitment postcode(s) [4] 5913 0
3128
Recruitment postcode(s) [5] 5914 0
3084
Recruitment postcode(s) [6] 5915 0
2310
Recruitment postcode(s) [7] 5916 0
2050
Recruitment postcode(s) [8] 5919 0
3222
Recruitment postcode(s) [9] 5920 0
2170
Recruitment postcode(s) [10] 10470 0
4066 - Auchenflower
Recruitment postcode(s) [11] 15026 0
5000 - Adelaide
Recruitment postcode(s) [12] 15027 0
2050 - Camperdown
Recruitment postcode(s) [13] 15028 0
6009 - Nedlands
Recruitment postcode(s) [14] 15029 0
4215 - Southport
Recruitment postcode(s) [15] 26750 0
3004 - Prahran
Recruitment outside Australia
Country [1] 4550 0
New Zealand
State/province [1] 4550 0
Canterbury
Country [2] 4551 0
New Zealand
State/province [2] 4551 0
Auckland
Country [3] 4552 0
New Zealand
State/province [3] 4552 0
Otago
Country [4] 4553 0
New Zealand
State/province [4] 4553 0
Wellington
Country [5] 4554 0
New Zealand
State/province [5] 4554 0
Waikato

Funding & Sponsors
Funding source category [1] 285998 0
Charities/Societies/Foundations
Name [1] 285998 0
MS Research Australia
Country [1] 285998 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
MS Research Australia
Address
MS Research Australia
PO Box 625 North Sydney NSW 2059
Level 19 Northpoint, 100 Miller St, North Sydney, NSW, 2060
Country
Australia
Secondary sponsor category [1] 284948 0
None
Name [1] 284948 0
Address [1] 284948 0
Country [1] 284948 0
Other collaborator category [1] 277143 0
Other Collaborative groups
Name [1] 277143 0
Neuroscience Trials Australia
Address [1] 277143 0
a wholly owned subsidary of The Florey Institute for Neuroscience and Mental Health
Melbourne Brain Centre- Austin Campus
245 Burgundy St
Heidelberg VIC
3084
Country [1] 277143 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288044 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 288044 0
Ethics committee country [1] 288044 0
Australia
Date submitted for ethics approval [1] 288044 0
29/08/2012
Approval date [1] 288044 0
03/10/2012
Ethics approval number [1] 288044 0
HREC_12_MH_218
Ethics committee name [2] 288308 0
Bellberry
Ethics committee address [2] 288308 0
Ethics committee country [2] 288308 0
Australia
Date submitted for ethics approval [2] 288308 0
26/09/2012
Approval date [2] 288308 0
12/11/2012
Ethics approval number [2] 288308 0
2012-09-1037
Ethics committee name [3] 288309 0
Tasmanian Health and Medical Human Research Ethics Committee
Ethics committee address [3] 288309 0
Ethics committee country [3] 288309 0
Australia
Date submitted for ethics approval [3] 288309 0
15/10/2012
Approval date [3] 288309 0
13/12/2012
Ethics approval number [3] 288309 0
H9912851
Ethics committee name [4] 288310 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [4] 288310 0
Ethics committee country [4] 288310 0
Australia
Date submitted for ethics approval [4] 288310 0
09/11/2012
Approval date [4] 288310 0
Ethics approval number [4] 288310 0
Ethics committee name [5] 293495 0
Central Health and Disability Ethics Committee
Ethics committee address [5] 293495 0
Ethics committee country [5] 293495 0
New Zealand
Date submitted for ethics approval [5] 293495 0
03/10/2012
Approval date [5] 293495 0
07/01/2013
Ethics approval number [5] 293495 0
12/CEN/44
Ethics committee name [6] 296644 0
Calvary Health Care Human Research Ethics Committee
Ethics committee address [6] 296644 0
Ethics committee country [6] 296644 0
Australia
Date submitted for ethics approval [6] 296644 0
13/04/2016
Approval date [6] 296644 0
30/05/2016
Ethics approval number [6] 296644 0
EC00302
Ethics committee name [7] 296645 0
Uniting Care Health Human Research Ethics Committee
Ethics committee address [7] 296645 0
Ethics committee country [7] 296645 0
Australia
Date submitted for ethics approval [7] 296645 0
10/02/2014
Approval date [7] 296645 0
10/04/2014
Ethics approval number [7] 296645 0
EC00374

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

Contacts
Principal investigator
Name 34704 0
A/Prof Helmut Butzkueven
Address 34704 0
Ms and NeuroImmunology Unit, Level 6, Alfred Centre, The Alfred Hospital, 99 Commercial Road, Melbourne VIC 3004 Australia
Country 34704 0
Australia
Phone 34704 0
+61 3 990 30640
Fax 34704 0
Email 34704 0
[email protected]
Contact person for public queries
Name 17951 0
Julia Morahan
Address 17951 0
MS Research Australia Level 19 Northpoint 100 Miller Street North Sydney NSW 2060
Country 17951 0
Australia
Phone 17951 0
+61 2 8413 7906
Fax 17951 0
Email 17951 0
[email protected]
Contact person for scientific queries
Name 8879 0
Helmut Butzkueven
Address 8879 0
MS Research Australia, PO Box 625, Sydney NSW 2059 AUSTRALIA
Country 8879 0
Australia
Phone 8879 0
+61 2 8413 7906
Fax 8879 0
Email 8879 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
Data will not be shared at this point.


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
SourceTitleYear of PublicationDOI
EmbaseUpdate on clinically isolated syndrome.2015https://dx.doi.org/10.1016/j.lpm.2015.03.002
EmbaseOn the nature of evidence and 'proving' causality: Smoking and lung cancer vs. sun exposure, vitamin D and multiple sclerosis.2018https://dx.doi.org/10.3390/ijerph15081726
EmbaseDoes the environment influence multiple sclerosis pathogenesis via UVB light and/or induction of vitamin D?.2019https://dx.doi.org/10.1016/j.jneuroim.2018.05.006
EmbaseImmunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis.2020https://dx.doi.org/10.1111/bph.15201
EmbaseEnvironmental risk factors in multiple sclerosis: bridging Mendelian randomization and observational studies.2022https://dx.doi.org/10.1007/s00415-022-11072-4
N.B. These documents automatically identified may not have been verified by the study sponsor.