Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001752853
Ethics application status
Approved
Date submitted
23/10/2021
Date registered
21/12/2021
Date last updated
21/12/2021
Date data sharing statement initially provided
21/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Sun-D Trial: the effect of high SPF sunscreen application on vitamin D
Scientific title
The Sun-D Trial: the effect of high SPF sunscreen application on vitamin D in Australian adults
Secondary ID [1] 305596 0
[1] Sponsor project number: P3755
Secondary ID [2] 305901 0
[2] Grant Application ID: 2006773
Universal Trial Number (UTN)
U1111-1270-5917
Trial acronym
Sun-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vitamin D deficiency 324029 0
Condition category
Condition code
Metabolic and Endocrine 321534 321534 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We plan a two-arm open-label RCT with a one-year intervention phase to assess the effect of high SPF sunscreen application on vitamin D. Participants will be recruited from the four eastern states of Australia (QLD, NSW, VIC & TAS) and the intervention will be self-administered. Participants will be randomly assigned to sunscreen and control groups. At baseline, both groups will be provided with advice about sun protection during planned outdoor activities will be provided at enrolment. This advice will be based on existing public health recommendations from Cancer Council Australia. The advice will be developed by the principle investigator and project manager in collaboration with the extended investigator team. It will be provided to all participants via email, along with the notification about their study group assignment.
The intervention group will be provided with a 1-year supply of a broad-spectrum SPF 50+ sunscreen, and asked to apply it to all body parts uncovered by clothing on all days when the ultraviolet index (UVI) is forecast to reach 3. They will be asked to view an animated video clip that describes when and how to apply the sunscreen. Study sunscreen has been chosen from the range of products commercially available in Australia. Two sunscreen products will be purchased from Key Pharmaceuticals: Hamilton Active Family SPF 50+, and Hamilton Everyday Face 50+. All participants in the intervention group will be supplied with Hamilton Active Family SPF 50+ (500 mL). A separate facial sunscreen will be offered and supplied if preferred; Hamilton Everyday Face SPF 50+ (75gm).
Weekly text and/or email reminders, regular phone contact, and access to a closed Facebook group will support participants in the active group to comply with the intervention. Weekly messages will alert participants to the UVI in their area, and they will also be asked to download and familiarize themselves with the free Sunsmart app. Phone contact will be made by study staff after the first two weeks, and then bi-monthly to identify barriers to sunscreen application and suggest solutions. Participation in a closed Facebook group will provide access to videos and hints about sunscreen application, sunscreen and sun exposure facts and an additional opportunity for participants to ask questions.
All participants will be asked to complete short online monthly surveys about their sunscreen use, clothing, and time outdoors. Those in the sunscreen group will be asked about use of study sunscreen and any additional sunscreen used.

Compliance will be calculated as the number of days applied (using self-reported frequency from the monthly surveys) divided by the number expected (estimated number of days where the forecast maximum UVI at the closest town was =3). Participants will also be asked to return bottles to be weighed.
Intervention code [1] 321999 0
Prevention
Comparator / control treatment
Control group: Will be asked to continue usual discretionary sunscreen use. Both groups will receive standard advice about sun protection during planned outdoors activities at the start of the study. The controls will receive no further intervention.
Control group
Active

Outcomes
Primary outcome [1] 329299 0
h25 hydroxyvitamin vitamin D (25(OH)D), measured by a liquid chromatography tandem mass spectroscopy method.
Timepoint [1] 329299 0
Blood samples will be collected at baseline (winter to early spring: Jun – Sept 2022), end of summer (Feb – March 2023), and at the end of the intervention phase (winter to early spring: Jul – Sept 2023). All samples will be analysed at the end of the study (Oct-Dec 2023). Results will be used to compare concentrations in the active and control groups at the end of summer and winter, and the effect of sunscreen on the change over time.
Secondary outcome [1] 402056 0
Actinic skin lesions during the trial and for up to the following 4 years.
Timepoint [1] 402056 0
Collected using linkage to the Medicare Benefits Schedule for consenting participants. The initial linkage will occur approximately 6 to 12 months after the intervention phase ends. Subsequent linkage will depend on funding.

Eligibility
Key inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provide electronic consent to participate
• Willing to comply with all study procedures and be available for the duration of the study
• Aged 30 to 65
• Resident of Queensland, New South Wales, Victoria or Tasmania
• Fitzpatrick skin type 1 to 4
Minimum age
30 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
People will be excluded if they are unable to provide consent or unable to communicate well enough in English to understand study requirements.
In addition, they will be excluded if they:
• Have a history of allergic skin reaction
• Have an autoimmune condition that affects the skin, such as psoriasis, lupus of the skin, scleroderma
• Have a history of melanoma within the past 5 years
• Are currently using sunscreen on a regular basis (i.e., > 2 days per week), excluding makeup or moisturiser with max SPF 15+ on the face
• Are taking or plan to start taking > 400 IU/day of supplementary vitamin D
• Do not have a phone
• Do not have access to electronic device suitable for survey completion and receiving reminders.

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)
The allocation sequence will be generated by an external statistician and uploaded to the database, where it will not be visible to study staff or investigators. Once all baseline components are returned the database will automatically apply the next record in the allocation sequence (within the relevant stratum).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised using computer-generated permuted block randomisation within strata defined according to state of residence (QLD, NSW, VIC, TAS), age (30-44, 45-64), and sex (M, F).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
SAMPLE SIZE: We have based our sample size calculations on the ANCOVA analyses, considering the following factors:
(1) A minimum difference in 25(OH)D concentration between treatment groups of 10 nmol/L; this is beyond the margin of assay error and a smaller difference is unlikely to be clinically relevant.
(2) 90% power and 5% significance using a one-tailed test. A one-tailed test is appropriate because if sunscreen use increases 25(OH)D concentration this will not be of clinical or public health relevance (given the very high 25(OH)D needed before toxicity occurs).
(3) Correlation between baseline and subsequent 25(OH)D values of 0.6 and standard deviation of 20 nmol/L: Based on a study in which 25(OH)D was measured on 333 participants from Brisbane and Canberra in all 4 seasons (R Lucas, personal communication).
(4) Non-compliance in the intervention group of 20%, and 10% uptake of daily sunscreen application in the control group
(5) Loss to follow-up of 20%.
The sample size required per group is 115. We require fully powered analyses within tertiles of ambient UVR and baseline 25(OH)D in order to devise appropriate public health and clinical messages. Thus the total sample size to be recruited is 345 per group (690 in total). With 552 participants (80%) completing the study the non-inferiority margin (90% power, a=0.05) is 4.5 nmol/L.

PRIMARY ANALYSES: Our main analyses will follow an intention-to-treat approach. 25(OH)D values in the Australian population are approximately normally distributed so we will model 25(OH)D as a continuous outcome using longitudinal analysis of covariance (ANCOVA). We will include treatment group (daily sunscreen or control), time, and the interaction between treatment and time to estimate the difference in 25(OH)D concentration between treatment groups at the end of summer and at the end of winter. This method has been shown to reliably estimate the effect of treatment, accounting for any differences in the baseline value of the outcome measure.35 All models will be adjusted for the variables used to stratify the randomisation and will include baseline 25(OH)D concentration as a covariate and participant as a random effect.
We will perform the analyses within the whole cohort and separately within tertiles defined according to: (1) average ambient UVR; and (2) baseline 25(OH)D concentration.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2022
Actual
Date of last participant enrolment
Anticipated
1/08/2022
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
690
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,TAS,VIC

Funding & Sponsors
Funding source category [1] 309960 0
Government body
Name [1] 309960 0
National Health and Medical Research Council
Country [1] 309960 0
Australia
Primary sponsor type
Other
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Rd, Herston, QLD 4006
Country
Australia
Secondary sponsor category [1] 311007 0
None
Name [1] 311007 0
Address [1] 311007 0
Country [1] 311007 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309675 0
'Queensland Institute of Medical Research Berghofer Human Research Ethics Committee
Ethics committee address [1] 309675 0
300 Herston Rd, Herston, QLD 4006
Ethics committee country [1] 309675 0
Australia
Date submitted for ethics approval [1] 309675 0
17/08/2021
Approval date [1] 309675 0
04/10/2021
Ethics approval number [1] 309675 0
P3755

Summary
Brief summary
Finding the balance between the risks and benefits of sun exposure is extremely challenging. The Cancer Council Australia and other organisations now advise daily sunscreen use to reduce UV radiation-induced damage arising from incidental exposure. Sunscreen blocks vitamin D production in experimental settings but there are no data about the effect of frequent application of high SPF sunscreens in community settings. Despite this, there is a widely held perception that using sunscreen will increase the risk of vitamin D deficiency and this is undermining skin cancer prevention messages.
We plan a two-arm open-label RCT with a one-year intervention phase. The primary aim is to determine whether participants randomised to provision of a broad-spectrum SPF 50+ sunscreen, and advice to apply it to all body parts uncovered by clothing on all days when the UVI is forecast to reach 3, have a lower mean 25 hydroxyvitamin D (25(OH)D) concentration at the end of either summer or winter than those randomised to usual discretionary sunscreen use. If daily sunscreen use reduces 25(OH)D concentration, we will model the impact on the prevalence of vitamin D deficiency in Australia to assess the public health significance of the change
Trial website
www.qimrberghofer.edu.au/sund/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114998 0
Prof Rachel Neale
Address 114998 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Qld 4006
Country 114998 0
Australia
Phone 114998 0
+61 7 3845 3598
Fax 114998 0
+61 7 3845 3502
Email 114998 0
[email protected]
Contact person for public queries
Name 114999 0
Prof Rachel Neale
Address 114999 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Qld 4006
Country 114999 0
Australia
Phone 114999 0
+61 7 3845 3598
Fax 114999 0
+61 7 3845 3502
Email 114999 0
[email protected]
Contact person for scientific queries
Name 115000 0
Prof Rachel Neale
Address 115000 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Qld 4006
Country 115000 0
Australia
Phone 115000 0
+61 7 3845 3598
Fax 115000 0
+61 7 3845 3502
Email 115000 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
IPD will not be publicly available. We do not have human research ethics committee approval for public release of information


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.