Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Non-melanoma Skin Cancer
Conditions
Brief summary
A common long-term side effect of anti-rejection (immunosuppressant) medications is skin cancer. This pilot clinical trial evaluates the feasibility of conducting a larger pivotal trial to examine the efficacy and safety of nicotinamide for prevention of keratinocyte carcinoma in solid organ transplant recipients. This pilot trial will transition into the pivotal trial if all feasibility targets are met.
Interventions
DRUGNicotinamide
Oral nicotinamide (500 mg) twice daily for at least 52 weeks
DRUGPlacebo oral capsule
Matching placebo taken twice daily for at least 52 weeks
Sponsors
Canadian Institutes of Health Research (CIHR)
The Kidney Foundation of Canada
NOW Foods
Natural Life Nutrition
Women's College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old 2. Kidney, liver, heart, or lung transplant at least two years ago 3. History of at least one prior histologically-confirmed keratinocyte carcinoma or squamous cell carcinoma in situ 4. Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or tacrolimus) 5. Able to attend follow-up visits 6. Able to speak and understand English (only for cognitive substudy)
Exclusion criteria
1. Use of mTOR inhibitor (sirolimus, everolimus) within the past 12 weeks 2. Biopsy-confirmed acute rejection episode within the past 12 weeks 3. Active liver disease (elevated AST or ALT \>3 times normal) 4. Severe renal failure (estimated glomerular filtration rate \<20 mL/min/1.73 m2) 5. Current carbamazepine or primidone use 6. Pregnancy and lactation 7. Gorlin syndrome or other genetic skin cancer syndrome 8. Solid organ or hematologic malignancy, invasive Stage II melanoma, Merkel cell carcinoma, or metastatic skin cancer within the past five years, or invasive Stage I melanoma within the past two years 9. Untreated localized skin cancer (invasive squamous cell carcinoma, basal cell carcinoma, or keratoacanthoma) at baseline (the patient can enrol after skin cancer treatment) 10. Use of nicotinamide or niacin (250 mg or more daily) within the past 12 weeks 11. Use of field therapy for actinic keratoses within the past 12 weeks 12. Initiation of systemic chemoprevention within the past 12 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility (pertaining to patient recruitment) | 1 year | Proportion of patients who consent to data linkage to provincial administrative databases |
| Feasibility (pertaining to appropriateness of eligibility criteria) | 1 year | Reasons for exclusion of screened patients |
| Feasibility (pertaining to adherence to intervention) | 1 year | Proportion of capsules returned, reasons for non-adherence |
| Feasibility (pertaining to adherence to follow-up assessments) | 1 year | Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation |
| Feasibility (pertaining to data linkage) | 1 year | Proportion of patients who consent to data linkage to provincial administrative databases |
| Preliminary pooled keratinocyte carcinoma event rate | 1 year | Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial. |
| Drug interactions | 1 week | Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 1 week. An increased level will be classified as clinically relevant if the transplant physician reduces the immunosuppressant dose in response to the increased drug level. |
| Serious adverse events | 1 year | Descriptive tabulation (preliminary safety) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of recruiting for neurocognitive substudy | 1 year | Proportion of enrolled participants who consent to participate in the neurocognitive substudy |
| Pooled standard deviation of serum phosphate levels (substudy) | 1 year | — |
| Baseline prevalence of cognitive impairment (substudy) | 1 year | Montreal Cognitive Assessment (MoCA) score \<26, scored out of 30. |
| Pooled standard deviation of MoCA test scores (substudy) | 1 year | Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function |
| Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy) | 1 year | Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory |
| Pooled standard deviation of Trail Making A and B test scores (substudy) | 1 year | Trail Making A and B, a visual attention test. This records the time (in seconds) to completion, with a faster time representing better cognitive function |
| Pooled standard deviation of Controlled Oral Word Association test scores (substudy) | 1 year | Controlled Oral Word Association, a verbal fluency test, measures the production of words belonging to the same letter. This records total number of words produced, with a higher number representing better verbal fluency. |
| Pooled standard deviation of Animal Naming Task scores (substudy) | 1 year | Animal Naming Task, a verbal fluency task, measures the total number of animals named in one minute, with a higher number representing better verbal fluency |
| Pooled standard deviation of cognitive test scores (substudy) | 1 year | Wechsler Adult Intelligence Scale - Revised, Digit Span subtest, a number sequencing memory test, measures the number of correctly repeated sequences with maximum score of 48. The higher score represents better cognitive function |
Countries
Canada
Outcome results
None listed