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Trial registered on ANZCTR


Registration number
ACTRN12612000628842
Ethics application status
Approved
Date submitted
6/06/2012
Date registered
12/06/2012
Date last updated
1/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of oral nicotinamide (vitamin B3) on nonmelanoma skin cancer incidence and actinic keratoses in renal transplant recipients: a randomised controlled trial
Scientific title
Randomised double blinded placebo controlled trial to assess the effect of oral nicotinamide on numbers of new nonmelanoma skin cancers in immune suppressed adult renal transplant recipients with a history of at least two histologically confirmed nonmelanoma skin cancers within the previous 12 months
Secondary ID [1] 280602 0
Nil
Universal Trial Number (UTN)
U1111-1131-4130
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonmelanoma skin cancer 286612 0
Actinic keratoses 286613 0
Basal cell carcinoma 286614 0
Cutaneous squamous cell carcinoma 286615 0
Cognitive function 286616 0
Kidney function after transplant 286648 0
Condition category
Condition code
Cancer 286885 286885 0 0
Non melanoma skin cancer
Neurological 286886 286886 0 0
Studies of the normal brain and nervous system
Renal and Urogenital 286937 286937 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral nicotinamide 500mg orally or placebo twice daily for 6 months
Intervention code [1] 284993 0
Prevention
Intervention code [2] 284994 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet containing calcium hydrogen phosphate anhydrous and cellulose- microcrystalline; taken orally twice daily for 6 months
Control group
Placebo

Outcomes
Primary outcome [1] 287240 0
Number of nonmelanoma skin cancers (basal cell carcinomas + cutaneous squamous cell carcinomas + squamous cell carcinomas in situ + keratoacanthomas) as assessed by histological examination of lesions detected during dermatological follow up
Timepoint [1] 287240 0
At 6 months after randomisation
Secondary outcome [1] 297710 0
Numbers of actinic keratoses assessed by clinical counting
Timepoint [1] 297710 0
At 0, 2, 4 and 6 months after randomisation
Secondary outcome [2] 297711 0
Numbers of nonmelanoma skin cancers confirmed by histology
Timepoint [2] 297711 0
At 2 and 4 months after randomisation
Secondary outcome [3] 297712 0
Numbers of basal cell carcinomas confirmed by histology
Timepoint [3] 297712 0
At 2, 4 and 6 months after randomisation
Secondary outcome [4] 297713 0
Numbers of cutaneous squamous cell carcinomas (including squamous cell carcinomas in situ and keratoacanthomas) confirmed by histology
Timepoint [4] 297713 0
At 2, 4 and 6 months after randomisation
Secondary outcome [5] 297714 0
Skin cancer recurrences, occurring at sites of previously histologically confirmed skin cancer, assessed by histology
Timepoint [5] 297714 0
Skin cancers recurring at any timepoint during the 6 month study period
Secondary outcome [6] 297715 0
Skin tumour markers of skin cancer proliferation, differentiation, apoptosis, immune cell infiltration and DNA damage assessed with immunohistochemistry; SCC differentiation and BCC subtype assessed by histology
Timepoint [6] 297715 0
On skin cancers developing at any timepoint during the 6 month study period
Secondary outcome [7] 297716 0
Safety profile of oral nicotinamide on patient and graft outcomes in renal transplant recipients, assessed by serum creatinine and eGFR, full blood count, electrolytes, liver function tests; urinary protein
Timepoint [7] 297716 0
At baseline, 2 weeks, 4 weeks, 2, 4 and 6 months after randomisation
Secondary outcome [8] 297741 0
Change in cognitive function assessed with standardised neuropsychological tests in the cognitive domains of memory, concentration, attention and executive function
-Hopkins Verbal Learning Test Revised (HVLT-R) (Brandt, 1991).

-Controlled Oral Word Association (COWA) (Spreen et al, 1998).

-Stroop Color and Word Test (Spreen and Strauss, 1998).

-Trail Making A & B (Reitan, 1955).
Timepoint [8] 297741 0
At baseline and 6 months after randomisation
Secondary outcome [9] 297818 0
Change in self-reported quality of life, assessed by:

-EORTC QLQ-C30 Cognitive Function items, PROMIS cognitive abilities item pool, cognitive general concerns item pool
-PROMIS fatigue item pool
-PROMIS anxiety item pool
-PROMIS depression item pool
-PROMIS Global Health Short Form for global health perception
Timepoint [9] 297818 0
At baseline and 6 months after randomisation

Eligibility
Key inclusion criteria
1. Prior renal transplant performed more than 12 months ago.
2. Current immune suppression.
3. Past history of at least two histologically confirmed nonmelanoma skin cancers within the past 12 months.

Equivalent to year 8 spoken and written English skills are required to participate in the cognitive component of the study. Patients with inadequate English skills may still participate in the other aspects of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Recent transplant less than 12 months ago.
2. Unstable renal function.
3. Treatment for acute rejection in the past 3 months.
4. Significant liver disease (transaminases >3x normal), severe cardiac disease
5. Internal malignancy, metastatic SCC or invasive melanoma within the past 5 years.
6. Need for ongoing carbamazepine use (possible interaction with nicotinamide).
7. Patients unavailable for follow up for the duration of the study because of general frailty, geographical or social reasons.
8. Gorlin’s syndrome or other genetic skin cancer syndrome.
9. Huge numbers of current skin cancers or large areas of confluent skin cancer at baseline preventing accurate assessment and counting of new skin cancers; field treatment for AKs within the past 4 weeks, preventing accurate assessment of AKs.
10. Pregnancy or lactation (any women of childbearing potential will be required to use contraception throughout the study).
11. Patients commenced on acitretin or other oral retinoids, or mTOR inhibitors within the past 6 months;
12. Patients taking supplemental nicotinamide within the past 4 weeks.

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)
All eligible patients enrolled in the study will be enetered into the central randomisation system. The patient number assigned at the time of randomisation will be the primary identifier for the patient. Randomisation will be performed by the NHMRC Clinical Trials Centre which will provide a centralised tele-randomisation service that will randomly allocate patients to nicotinamide or placebo groups in a 1:1 ratio stratified by gender, baseline skin cancer count and use of oral retinoids and/or mTOR inhibitors. The pharmacist will provide the drug kit allocated by the system for the patient, recording the kit number in the pharmacy log. The study number, patient name and MRN will then be written on the medication bottle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to nicotinamide or placebo groups in a 1:1 ratio using a permuted blocks method stratified by gender, baseline skin cancer count (6 or more versus 2-5 previous skin cancers), and whether or not they are taking oral retinoids, or mTOR inhibitors
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 285360 0
Other
Name [1] 285360 0
Australasian College of Dermatologists Scientific Research Fund
Address [1] 285360 0
The Australasian College of Dermatologists
Suite 2A, Level 2
9 Blaxland Road
RHODES NSW 2138
Country [1] 285360 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Sydney Medical School,
University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 284215 0
None
Name [1] 284215 0
Address [1] 284215 0
Country [1] 284215 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287375 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 287375 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 287375 0
Australia
Date submitted for ethics approval [1] 287375 0
Approval date [1] 287375 0
13/02/2012
Ethics approval number [1] 287375 0
HREC/11/RPAH/337

Summary
Brief summary
This study aims to assess the effect of nicotinamide (vitamin B3) on nonmelanoma skin cancer incidence in renal transplant recipients. Who is it for? You may be eligible to join this study if you are aged 18 years or more and have had a renal transplant more than 12 months ago. You should be experiencing current immune suppression and have a past history of at least two confirmed nonmelanoma skin cancers within the past 12 months. Trial details Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will take two 500mg nicotinamide (vitamin B3) tablets daily for 6 months, whilst those in the other group will take two placebo (inactive) tablets daily instead. Participants will not know which group they are in until the end of the trial. Participants will be regularly assessed over the treatment period to determine the efficacy of nicotinamide in preventing nonmelanoma skin cancers and the safety of this treatment in renal transplant recipients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34252 0
Prof Diona Damian
Address 34252 0
Dermatology, GH3 Royal Prince Alfred Hospital Missenden Rd Camperdown NSW 2050
Country 34252 0
Australia
Phone 34252 0
+612 9515 8295
Fax 34252 0
Email 34252 0
diona.damian@sswahs.nsw.gov.au
Contact person for public queries
Name 17499 0
Prof Professor Diona Damian
Address 17499 0
Dermatology, GH3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 17499 0
Australia
Phone 17499 0
+612 9515 8295
Fax 17499 0
+612 9565 1048
Email 17499 0
diona.damian@sswahs.nsw.gov.au
Contact person for scientific queries
Name 8427 0
Prof Professor Diona Damian
Address 8427 0
Dermatology, GH3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 8427 0
Australia
Phone 8427 0
+612 9515 8295
Fax 8427 0
+612 9565 1048
Email 8427 0
diona.damian@sswahs.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary