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.
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
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
396
Oral nicotinamide (500 mg) twice daily
Matching placebo capsule twice daily
University of Calgary
Calgary, Alberta, Canada
NOT_YET_RECRUITINGUniversity of Alberta
Edmonton, Alberta, Canada
RECRUITINGVancouver General Hospital
Vancouver, British Columbia, Canada
RECRUITINGSt. Paul's Hospital
Vancouver, British Columbia, Canada
RECRUITINGThe Ottawa Hospital
Ottawa, Ontario, Canada
RECRUITINGToronto General Hospital
Toronto, Ontario, Canada
RECRUITINGWomen's College Hospital
Toronto, Ontario, Canada
RECRUITINGTime to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma)
Time frame: Up to 208 weeks
Time to first invasive squamous cell carcinoma during follow-up
Time frame: Up to 208 weeks
Time to first basal cell carcinoma during follow-up
Time frame: Up to 208 weeks
Time to multiple keratinocyte carcinomas over follow-up
Time frame: Up to 208 weeks
Occurrence of adverse events during follow-up
Overall and by body system, frequency, seriousness, and severity
Time frame: 208 weeks
Acute graft rejection (biopsy-confirmed)
Adverse event
Time frame: 208 weeks
Graft loss or retransplantation
Adverse event
Time frame: 208 weeks
High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment
Adverse event
Time frame: 208 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score
Time frame: 52 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score
Time frame: 104 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score
Time frame: 156 weeks
Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).
Time frame: 208 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest
Time frame: 52 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest
Time frame: 104 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest
Time frame: 156 weeks
Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest
Time frame: 208 weeks
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