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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Actinic keratoses

Condition category

Condition code

Skin

Dermatological conditions

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Oral nicotinamide 500mg daily for four months

Intervention code [1]

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]

Reduction in total actinic keratosis (AK) count at 2 and 4 months from baseline

Timepoint [1]

2 and 4 months

Secondary outcome [1]

Nil

Timepoint [1]

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Cancer Council NSW

Address [1]

153 Dowling Street
Woolloomooloo, NSW 2011
PO Box 572
Kings Cross NSW 1340
Australia

Country [1]

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]

Individual

Name [1]

Diona Damian

Address [1]

Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney South West Area Health Service (SSWAHS) Ethics Committee

Ethics committee address [1]

Building 92 Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

09/08/2010

Ethics approval number [1]

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

Prof Diona Damian

Address

Dermatology, GH3
Royal Prince Alfred Hospital
Camperdown NSW 2050

Country

Australia

Phone

+612 9515 8295

Fax

+612 9565 1048

[email protected]

Contact person for public queries

Name

Diona Damian

Address

Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050

Country

Australia

Phone

612 9515 8295

Fax

612 9565 1048

[email protected]

Contact person for scientific queries

Name

Diona Damian

Address

Dermatology
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050

Country

Australia

Phone

612 9515 8295

Fax

612 9565 1048

[email protected]

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

Source	Title	Year of Publication	DOI
Dimensions AI	Oral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials	2012	https://doi.org/10.1038/jid.2011.459

N.B. These documents automatically identified may not have been verified by the study sponsor.

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