Trial Review

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The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

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Trial registered on ANZCTR


Registration number
ACTRN12610000689077
Ethics application status
Approved
Date submitted
19/08/2010
Date registered
20/08/2010
Date last updated
29/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised, double-blind, placebo controlled study to assess efficacy of oral nicotinamide (500mg daily) in the treatment and prevention of actinic keratoses.
Scientific title
Effect of nicotinamide versus placebo on numbers of actinic keratoses
Secondary ID [1] 252515 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Actinic keratoses 258004 0
Condition category
Condition code
Skin 258173 258173 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral nicotinamide 500mg daily for four months
Intervention code [1] 257049 0
Treatment: Drugs
Comparator / control treatment
Placebo tablets (lactose tablets idetical in appearance and size to nicotinamide tablets but without active ingredient) daily for four months.
Control group
Placebo

Outcomes
Primary outcome [1] 259034 0
Reduction in total actinic keratosis (AK) count at 2 and 4 months from baseline
Timepoint [1] 259034 0
2 and 4 months
Secondary outcome [1] 265295 0
Nil
Timepoint [1] 265295 0
Nil

Eligibility
Key inclusion criteria
Men and women > 18 years old.
Symmetrically distributed non-hyperkeratotic AKs on face / scalp/ upper limbs.
Minimum of 4 AKs in one or more treatment areas.
Patients have received no other treatments for AKs within the last month.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Under 18 years old
Pregnant or lactating
Taking immunosuppressive or photosensitising medications
Immune suppressive concurrent illness (eg, human immunodeficiency virus- HIV- infection)
Malignancy (excluding nonmelanoma skin cancer) in the previous 5 years
Taking nicotinamide supplements within the last month
Patients unable to attend for regular follow up
Patients with active dermatitis in assessment areas
Liver disease (although hepatic effects of nicotinamide are rare, in contrast to nicotinic acid)
Currently taking carbamazepine (case reports of interaction with nicotinamide)

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)
Sequentially numbered bottles (ie, numbered containers) will be randomised at source with patients and observers blinded to assignment. The person determing whether a subject is eligible for inclusion in the trial will be unaware, when this decision is made, as to which group the subject would be allocated. The randomisation code will be unbroken until the final patient completes the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Unstratified, randomised blocks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/08/2010
Actual
1/09/2010
Date of last participant enrolment
Anticipated
Actual
1/03/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257497 0
Charities/Societies/Foundations
Name [1] 257497 0
Cancer Council NSW
Country [1] 257497 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Sydney South West Area Health Service (SSWAHS) Ethics Committee
Level 3 Building 92
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country
Australia
Secondary sponsor category [1] 256729 0
Individual
Name [1] 256729 0
Diona Damian
Address [1] 256729 0
Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country [1] 256729 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259524 0
Sydney South West Area Health Service (SSWAHS) Ethics Committee
Ethics committee address [1] 259524 0
Building 92 Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Ethics committee country [1] 259524 0
Australia
Date submitted for ethics approval [1] 259524 0
Approval date [1] 259524 0
09/08/2010
Ethics approval number [1] 259524 0
09/RPAH/2

Summary
Brief summary
More than 50% of all Caucasian Australians will develop non-melanoma skin cancer (NMSC) during their lifetime, and more than one in 30 will develop melanoma. Ultraviolet radiation (UVR) from sunlight is the major cause of NMSC. In humans, both the ultraviolet A (UVA) and ultraviolet B (UVB) wavebands cause immunosuppression and DNA damage and therefore both UVA and UVB are likely to contribute to induction and development of NMSC. Broad-spectrum sunscreens, which filter both UVB and UVA can reduce UV immunosuppression, but sunscreens are generally much better at preventing sunburn than immunosuppression. As immunosuppression can occur with less than half the amount of UV needed to cause sunburn, the immune protection afforded by sunscreens “in the field” is likely to be low.
Oral nicotinamide (vitamin B3) is available as an over-the-counter vitamin supplement and has been effective for over 50 years in the treatment of autoimmune and inflammatory skin disorders including bullous pemphigoid and rosacea. Unlike nicotinic acid, nicotinamide does not cause significant vasodilation or flushing and has few or no potential side effects. The most commonly used dose in autoimmune blistering disorders is 1500mg daily, with these patients often taking nicotinamide for several months. Adverse effects are exceptionally rare at these doses.
In mice, nicotinamide reduces skin cancer numbers by 60% when applied as a 2.5% lotion. Our group has demonstrated that nicotinamide lotion completely prevents UV immunosuppression when applied in a double-blinded placebo-controlled manner to the backs of healthy human volunteers. We subsequently found that oral nicotinamide was also immune protective in healthy, Mantoux-positive volunteers, without adverse effects, at doses of either 500mg daily or 1500mg daily. Recently, we tested topical 1% nicotinamide on numbers of actinic keratoses, and found a significant reduction in numbers of keratoses at 3 months compared to placebo. We now plan to assess the effects of oral nicotinamide at an intermediate dose (500mg daily) on AK numbers. We hypothesise that nicotinamide will be well-tolerated, and could be used together with sunscreens to reduce UV immunosuppression and potentially treat or prevent actinic keratosis, premalignant lesions which act as a surrogate marker for squamous cell skin cancers.
Trial website
Trial related presentations / publications
Surjana D, Halliday GM, Damian DL. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. [Invited review] Journal of Nucleic Acids Article ID 157591, 2010

Park J, Halliday GM, Surjana D, Damian DL. Nicotinamide prevents ultraviolet radiation-induced cellular energy loss. Photochemistry and Photobiology 86:942-8, 2010

Damian DL. Photoprotective effects of nicotinamide [Invited review]. Photochemical and Photobiological Sciences 9: 578-85, 2010

Moloney FJ, Vestergaard ME, Radojkovic BL, Damian DL. Randomised, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses. British Journal of Dermatology 162:1138-9, 2010

Sivapirabu G, Yiasemides E, Halliday GM, Park J, Damian DL. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. British Journal of Dermatology 161:1357-1364, 2009

Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 30:101-5, 2009

Damian DL, Patterson CRS, Stapelberg M, Park J, Barnetson RStC, Halliday GM. Ultraviolet radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. Journal of Investigative Dermatology 128:447-454, 2008
Public notes

Contacts
Principal investigator
Name 31546 0
Prof Diona Damian
Address 31546 0
Dermatology, GH3
Royal Prince Alfred Hospital
Camperdown NSW 2050
Country 31546 0
Australia
Phone 31546 0
+612 9515 8295
Fax 31546 0
+612 9565 1048
Email 31546 0
diona.damian@sswahs.nsw.gov.au
Contact person for public queries
Name 14793 0
Diona Damian
Address 14793 0
Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country 14793 0
Australia
Phone 14793 0
612 9515 8295
Fax 14793 0
612 9565 1048
Email 14793 0
diona.damian@sswahs.nsw.gov.au
Contact person for scientific queries
Name 5721 0
Diona Damian
Address 5721 0
Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country 5721 0
Australia
Phone 5721 0
612 9515 8295
Fax 5721 0
612 9565 1048
Email 5721 0
diona.damian@sswahs.nsw.gov.au

No information has been provided regarding IPD availability


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
Dimensions AIOral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials2012https://doi.org/10.1038/jid.2011.459
N.B. These documents automatically identified may not have been verified by the study sponsor.