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Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial

Phase 2
Active, not recruiting
Conditions
Non-melanoma Skin Cancer
Carcinoma, Squamous Cell
Carcinoma, Basal Cell
Interventions
Drug: Placebo oral capsule
Registration Number
NCT03769285
Lead Sponsor
Women's College Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
120
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NicotinamideNicotinamide-
PlaceboPlacebo oral capsule-
Primary Outcome Measures
NameTimeMethod
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

Drug interactions2 weeks

Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 2 weeks. This measurement will be dropped if all cases of clinically relevant drug interactions manifest at 1 week in the first 20 enrolled participants.

Serious adverse events1 year

Descriptive tabulation (preliminary safety)

Preliminary pooled keratinocyte carcinoma event rate1 year

Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.

Secondary Outcome Measures
NameTimeMethod
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

Pooled standard deviation of serum phosphate levels (substudy)1 year
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.

Feasibility of recruiting for neurocognitive substudy1 year

Proportion of enrolled participants who consent to participate in the neurocognitive substudy

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

Baseline prevalence of cognitive impairment (substudy)1 year

Montreal Cognitive Assessment (MoCA) score \<26, scored out of 30.

Trial Locations

Locations (1)

Toronto General Hospital, University Health Network

🇨🇦

Toronto, Ontario, Canada

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