Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial (SPRINTR-Pilot)

Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: A Pilot, Placebo-controlled, Randomized Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Squamous Cell; Carcinoma, Basal Cell; Non-melanoma Skin Cancer
• Intervention / Treatment: Drug: Nicotinamide; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital, University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo oral capsule; Matching placebo taken twice daily for at least 52 weeks
Experimental: Nicotinamide	Drug: Nicotinamide; Oral nicotinamide (500 mg) twice daily for at least 52 weeks; Other Names: niacinamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility (pertaining to patient recruitment)	Proportion of patients who consent to data linkage to provincial administrative databases	1 year
Feasibility (pertaining to appropriateness of eligibility criteria)	Reasons for exclusion of screened patients	1 year
Feasibility (pertaining to adherence to intervention)	Proportion of capsules returned, reasons for non-adherence	1 year
Feasibility (pertaining to adherence to follow-up assessments)	Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation	1 year
Feasibility (pertaining to data linkage)	Proportion of patients who consent to data linkage to provincial administrative databases	1 year
Preliminary pooled keratinocyte carcinoma event rate	Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.	1 year
Drug interactions	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.	1 week
Drug interactions	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.	2 weeks
Serious adverse events	Descriptive tabulation (preliminary safety)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of recruiting for neurocognitive substudy	Proportion of enrolled participants who consent to participate in the neurocognitive substudy	1 year
Baseline prevalence of cognitive impairment (substudy)	Montreal Cognitive Assessment (MoCA) score <26, scored out of 30.	1 year
Pooled standard deviation of MoCA test scores (substudy)	Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function	1 year
Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)	Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory	1 year
Pooled standard deviation of Trail Making A and B test scores (substudy)	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	1 year
Pooled standard deviation of Controlled Oral Word Association test scores (substudy)	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.	1 year
Pooled standard deviation of Animal Naming Task scores (substudy)	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	1 year
Pooled standard deviation of cognitive test scores (substudy)	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	1 year
Pooled standard deviation of serum phosphate levels (substudy)		1 year

Collaborators and Investigators

• Sponsor: Women's College Hospital
• Collaborators: Canadian Institutes of Health Research (CIHR); The Kidney Foundation of Canada; NOW Foods; Natural Life Nutrition

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Squamous Cell; Skin Neoplasms; Carcinoma, Basal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: SPRINTR-Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If feasibility thresholds are met, this pilot trial will proceed to a larger pivotal trial. The study protocol for the pivotal trial will be published prior to completion of data collection. Beyond 2 years after completion of the pivotal trial, the cleaned, anonymized, participant-level dataset and statistical code will made available for sharing with external researchers upon approval of a study proposal describing the intended data usage.
• IPD Sharing Time Frame: 2 years after completion of the pivotal trial that follows this pilot trial
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No