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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05955924
Other study ID # SPRINTR-pivotal
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date August 28, 2023
Est. completion date August 2027

Study information

Verified date April 2024
Source Women's College Hospital
Contact Nihilkumar Dobariya, M.Pharm MSRA
Phone 416 351-3732
Email sprintr@wchospital.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 396
Est. completion date August 2027
Est. primary completion date August 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Nicotinamide
Oral nicotinamide (500 mg) twice daily
Placebo
Matching placebo capsule twice daily

Locations

Country Name City State
Canada University of Calgary Calgary Alberta
Canada University of Alberta Edmonton Alberta
Canada The Ottawa Hospital Ottawa Ontario
Canada University of Ottawa Heart Institute Ottawa Ontario
Canada Toronto General Hospital Toronto Ontario
Canada Women's College Hospital Toronto Ontario
Canada St. Paul's Hospital Vancouver British Columbia
Canada Vancouver General Hospital Vancouver British Columbia

Sponsors (4)

Lead Sponsor Collaborator
Women's College Hospital Canadian Institutes of Health Research (CIHR), NOW Foods, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma) Up to 208 weeks
Secondary Time to first invasive squamous cell carcinoma during follow-up Up to 208 weeks
Secondary Time to first basal cell carcinoma during follow-up Up to 208 weeks
Secondary Time to multiple keratinocyte carcinomas over follow-up Up to 208 weeks
Secondary Occurrence of adverse events during follow-up Overall and by body system, frequency, seriousness, and severity 208 weeks
Secondary Acute graft rejection (biopsy-confirmed) Adverse event 208 weeks
Secondary Graft loss or retransplantation Adverse event 208 weeks
Secondary High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment Adverse event 208 weeks
Secondary Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score 52 weeks
Secondary Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score 104 weeks
Secondary Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score 156 weeks
Secondary Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) 208 weeks
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN). 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN). 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN). 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN). 208 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest 52 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest 104 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest 156 weeks
Secondary Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest 208 weeks
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