Clinical trial NCT03769285: Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial
Official title: Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: A Pilot, Placebo-controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-melanoma Skin Cancer
Carcinoma, Squamous Cell
Carcinoma, Basal Cell
Lead sponsor: Women's College Hospital
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Kidney Foundation of Canada
name: NOW Foods
name: Natural Life Nutrition
First posted: 2018-12-07
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Feasibility (pertaining to patient recruitment)
timeFrame: 1 year
measure: Feasibility (pertaining to appropriateness of eligibility criteria)
timeFrame: 1 year
measure: Feasibility (pertaining to adherence to intervention)
timeFrame: 1 year
measure: Feasibility (pertaining to adherence to follow-up assessments)
timeFrame: 1 year
measure: Feasibility (pertaining to data linkage)
timeFrame: 1 year
measure: Preliminary pooled keratinocyte carcinoma event rate
timeFrame: 1 year
measure: Drug interactions
timeFrame: 1 week
measure: Drug interactions
timeFrame: 2 weeks
measure: Serious adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Feasibility of recruiting for neurocognitive substudy
timeFrame: 1 year
measure: Baseline prevalence of cognitive impairment (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of MoCA test scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of Trail Making A and B test scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of Controlled Oral Word Association test scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of Animal Naming Task scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of cognitive test scores (substudy)
timeFrame: 1 year
measure: Pooled standard deviation of serum phosphate levels (substudy)
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
Study officials:
affiliation: Women's College Hospital
name: An-Wen Chan, MD DPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Joseph Kim, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: