Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients - Pivotal Trial (SPRINTR)

Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: a Multicentre, Pragmatic Randomized Trial

As patients live longer after receiving an organ transplant, there is a need to reduce the long-term side effects of the drugs used to prevent organ rejection. In particular, long-term use of these drugs increases the risk of skin cancer. Skin cancer is now a leading cause of illness and disfigurement after kidney, liver, heart, and lung transplantation. Given the increased risk and burden of skin cancer in transplant recipients, prevention is critical.

Nicotinamide is a form of Vitamin B3 that has been shown to protect against skin cancer in the general population. However, it is unclear whether nicotinamide is effective among immune-suppressed transplant recipients. Investigators will conduct a clinical trial involving multiple transplant centres in Canada to evaluate whether oral nicotinamide (500 mg twice daily) is effective and safe for preventing skin cancer. Investigators will recruit 396 high-risk adult kidney, liver, heart, and lung transplant patients who have previously had at least one skin cancer. Patients will receive nicotinamide or sham tablets for up to 4 years. The results will inform efforts to improve the long-term health of transplant recipients.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Squamous Cell; Carcinoma, Basal Cell; Keratinocyte Carcinoma; Non-melanoma Skin Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Nicotinamide

Detailed Description

Improved survival after solid organ transplantation has created the need to better prevent the long-term adverse effects of immunosuppressant drugs in transplant survivors - particularly cancer development. Keratinocyte carcinoma (non-melanoma skin cancer) is by far the most common form of post-transplant malignancy and has a more aggressive clinical course than in the general population. Preventive measures are thus critical to reduce the burden of skin cancer in the high-risk transplant population.

Nicotinamide is a low-cost, commercially available, over-the-counter Vitamin B3 derivative that has been found to safely reduce the rate of keratinocyte carcinoma in immunocompetent patients with a history of skin cancer. It is unclear whether its efficacy and safety translate to the immunosuppressed transplant population.

Given this uncertainty, Investigators plan to build on our internal pilot study (N=120) to conduct the SPRINTR (Skin cancer PRevention with Nicotinamide in Transplant Recipients) pivotal trial to address these specific aims:

Primary question: Does oral nicotinamide (500 mg twice daily) reduce the rate of further keratinocyte carcinoma compared with placebo when used in addition to standard care for up to 208 weeks in high-risk solid organ transplant recipients?

Secondary questions:

1. What is the safety of nicotinamide when used in addition to standard care for up to 208 weeks in the transplant population?
2. What is the effect of nicotinamide on quality of life related to skin cancer?

Investigators will conduct a multicentre, pragmatic, parallel group, investigator- and patient-blinded, randomized trial with a superiority framework. This pivotal trial will evaluate the efficacy and safety of oral nicotinamide versus placebo to prevent further keratinocyte carcinoma in 396 high-risk solid organ transplant recipients. Data from our previous internal pilot study (N=120 participants) will be combined with data from the current pivotal trial (N=276 additional patients) in the final analysis.

• Study Type: Interventional
• Enrollment (Estimated): 396
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Stephanie Jewell, BSc. Hons; Phone Number: 2706 416 351-3732; Email: sprintr@wchospital.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • Not yet recruiting
      • University Of Calgary
      • Contact: Coralea Bignell; Email: coralea.bignell@albertahealthservices.ca
      • Principal Investigator: Ngam Lam
    • Edmonton, Alberta, Canada, T6G 2R3
      • Recruiting
      • University of Alberta
      • Principal Investigator: Sita Gourishankar
      • Contact: Kelly Kim; Email: kkim6@ualberta.ca
      • Sub-Investigator: Jaggi Rao
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Recruiting
      • St. Paul's Hospital
      • Principal Investigator: John Gill
      • Contact: Anushka Sood; Email: asood1@providencehealth.bc.ca
      • Sub-Investigator: Sheila Au
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver General Hospital
      • Contact: Natalie Ng; Email: natalie.ng@ubc.ca
      • Principal Investigator: Sunil Kalia
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Recruiting
      • The Ottawa Hospital
      • Contact: Christine Lennox; Email: clennox@ohri.ca
      • Principal Investigator: Jennifer Beecker
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital
      • Principal Investigator: An-Wen Chan
      • Contact: Marsida Stafa; Email: SPRINTR@wchospital.ca
    • Toronto, Ontario, Canada, M5S 1B2
      • Recruiting
      • Women's College Hospital
      • Principal Investigator: An-Wen Chan
      • Contact: Stephanie Jewell; Email: SPRINTR@wchospital.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Kidney, liver, heart, or lung transplant at least two years ago
• History of at least one prior histologically-confirmed keratinocyte carcinoma or squamous cell carcinoma in situ
• Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or tacrolimus)
• Able to attend follow-up visits

Exclusion Criteria:

• Use of nicotinamide or niacin (≥250 mg daily) within past 12 weeks
• Untreated localized skin cancer at baseline (patient can enrol after skin cancer treatment)
• Biopsy-confirmed acute rejection episode within the past 12 weeks
• Active liver disease (high AST >3 times or bilirubin >1.5 times)
• Severe kidney disease (estimated glomerular filtration rate <20 mL/min/1.73 m2)
• Solid organ or hematologic malignancy, invasive melanoma, Merkel cell carcinoma, or metastatic skin cancer within the past five years
• Pregnancy or lactation
• Need for ongoing carbamazepine or primidone
• Allergy to nicotinamide or any ingredient of the vitamin or placebo capsules

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
Experimental: Nicotinamide; Intervention Drug : Nicotinamide	Drug: Nicotinamide; Oral nicotinamide (500 mg) twice daily; Other Names: niacinamide
Placebo Comparator: Placebo; Intervention: Placebo Oral Capsule	Drug: Placebo; Matching placebo capsule twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma)	Up to 208 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first invasive squamous cell carcinoma during follow-up		Up to 208 weeks
Time to first basal cell carcinoma during follow-up		Up to 208 weeks
Time to multiple keratinocyte carcinomas over follow-up		Up to 208 weeks
Occurrence of adverse events during follow-up	Overall and by body system, frequency, seriousness, and severity	208 weeks
Acute graft rejection (biopsy-confirmed)	Adverse event	208 weeks
Graft loss or retransplantation	Adverse event	208 weeks
High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment	Adverse event	208 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score		52 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score		104 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score		156 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)		208 weeks
Neurocognitive substudy - Proportion of participants with cognitive impairment	As defined by the International Cognition and Cancer Task Force (T scores ≥2 standard deviations below the normative population mean on a single test, or ≥1.5 standard deviations below the mean on at least two tests, or both)	52 weeks
Neurocognitive substudy - Proportion of participants with cognitive impairment	As defined by the International Cognition and Cancer Task Force (T scores ≥2 standard deviations below the normative population mean on a single test, or ≥1.5 standard deviations below the mean on at least two tests, or both)	104 weeks
Neurocognitive substudy - Proportion of participants with cognitive impairment	As defined by the International Cognition and Cancer Task Force (T scores ≥2 standard deviations below the normative population mean on a single test, or ≥1.5 standard deviations below the mean on at least two tests, or both)	156 weeks
Neurocognitive substudy - Proportion of participants with cognitive impairment	As defined by the International Cognition and Cancer Task Force (T scores ≥2 standard deviations below the normative population mean on a single test, or ≥1.5 standard deviations below the mean on at least two tests, or both)	208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest		208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).		52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).		104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).		156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).		208 weeks

Collaborators and Investigators

• Sponsor: Women's College Hospital
• Collaborators: University Health Network, Toronto; Canadian Institutes of Health Research (CIHR); NOW Foods
• Investigators: Principal Investigator: An-Wen Chan, Women's College Hospital; Principal Investigator: Sang Joseph Kim, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The trial protocol and statistical code will be shared upon request. Beyond 18 months after trial completion, the anonymized participant-level dataset will made available for sharing with external researchers upon approval of a reasonable study proposal describing the intended data usage.
• IPD Sharing Time Frame: Beyond 18 months after trial completion.
• IPD Sharing Access Criteria: Data will be made available for sharing with external researchers upon approval of a well-defined study proposal that clearly outlines the intended use of the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; 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