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

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ClinicalTrials.gov Identifier: NCT05955924
Recruitment Status : Recruiting
First Posted : July 21, 2023
Last Update Posted : September 26, 2023
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
University Health Network, Toronto
NOW Foods
Information provided by (Responsible Party):
Women's College Hospital

Brief 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.


Condition or disease Intervention/treatment Phase
Non-melanoma Skin Cancer Carcinoma, Squamous Cell Carcinoma, Basal Cell Keratinocyte Carcinoma Drug: Nicotinamide Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 396 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicentre, parallel group, placebo-controlled, pragmatic randomized trial with 1:1 allocation and a superiority framework
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Matching placebo
Primary Purpose: Prevention
Official Title: Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: a Multicentre, Pragmatic Randomized Trial
Actual Study Start Date : August 28, 2023
Estimated Primary Completion Date : August 2027
Estimated Study Completion Date : August 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nicotinamide
Intervention Drug : Nicotinamide
Drug: Nicotinamide
Oral nicotinamide (500 mg) twice daily
Other Name: niacinamide

Placebo Comparator: Placebo
Intervention: Placebo Oral Capsule
Drug: Placebo
Matching placebo capsule twice daily




Primary Outcome Measures :
  1. Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma) [ Time Frame: Up to 208 weeks ]

Secondary Outcome Measures :
  1. Time to first invasive squamous cell carcinoma during follow-up [ Time Frame: Up to 208 weeks ]
  2. Time to first basal cell carcinoma during follow-up [ Time Frame: Up to 208 weeks ]
  3. Time to multiple keratinocyte carcinomas over follow-up [ Time Frame: Up to 208 weeks ]
  4. Occurrence of adverse events during follow-up [ Time Frame: 208 weeks ]
    Overall and by body system, frequency, seriousness, and severity

  5. Acute graft rejection (biopsy-confirmed) [ Time Frame: 208 weeks ]
    Adverse event

  6. Graft loss or retransplantation [ Time Frame: 208 weeks ]
    Adverse event

  7. High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment [ Time Frame: 208 weeks ]
    Adverse event

  8. Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [ Time Frame: 52 weeks ]
  9. Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [ Time Frame: 104 weeks ]
  10. Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [ Time Frame: 156 weeks ]
  11. Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [ Time Frame: 208 weeks ]
  12. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) [ Time Frame: 52 weeks ]
  13. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) [ Time Frame: 104 weeks ]
  14. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) [ Time Frame: 156 weeks ]
  15. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) [ Time Frame: 208 weeks ]
  16. Neurocognitive substudy - Proportion of participants with cognitive impairment [ Time Frame: 52 weeks ]
    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)

  17. Neurocognitive substudy - Proportion of participants with cognitive impairment [ Time Frame: 104 weeks ]
    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)

  18. Neurocognitive substudy - Proportion of participants with cognitive impairment [ Time Frame: 156 weeks ]
    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)

  19. Neurocognitive substudy - Proportion of participants with cognitive impairment [ Time Frame: 208 weeks ]
    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)

  20. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised [ Time Frame: 52 weeks ]
  21. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised [ Time Frame: 104 weeks ]
  22. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised [ Time Frame: 156 weeks ]
  23. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised [ Time Frame: 208 weeks ]
  24. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B [ Time Frame: 52 weeks ]
  25. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B [ Time Frame: 104 weeks ]
  26. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B [ Time Frame: 156 weeks ]
  27. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B [ Time Frame: 208 weeks ]
  28. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association [ Time Frame: 52 weeks ]
  29. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association [ Time Frame: 104 weeks ]
  30. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association [ Time Frame: 156 weeks ]
  31. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association [ Time Frame: 208 weeks ]
  32. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task [ Time Frame: 52 weeks ]
  33. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task [ Time Frame: 104 weeks ]
  34. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task [ Time Frame: 156 weeks ]
  35. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task [ Time Frame: 208 weeks ]
  36. 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 ]
  37. 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 ]
  38. 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 ]
  39. 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 ]
  40. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest [ Time Frame: 52 weeks ]
  41. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest [ Time Frame: 104 weeks ]
  42. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest [ Time Frame: 156 weeks ]
  43. Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest [ Time Frame: 208 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05955924


Contacts
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Contact: Nihilkumar Dobariya, M.Pharm MSRA 416 351-3732 ext 2706 sprintr@wchospital.ca

Locations
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Canada, Alberta
University of Calgary Not yet recruiting
Calgary, Alberta, Canada, T2N 1N4
University of Alberta Not yet recruiting
Edmonton, Alberta, Canada, T6G 2R3
Canada, British Columbia
Vancouver General Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
St. Paul's Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
The Ottawa Hospital Not yet recruiting
Ottawa, Ontario, Canada, K1Y 4E9
University of Ottawa Heart Institute Not yet recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Principal Investigator: An-Wen Chan         
Women's College Hospital Not yet recruiting
Toronto, Ontario, Canada, M5S 1B2
Contact: Nihil Dobariya       sprintr@wchospital.ca   
Principal Investigator: An-Wen Chan         
Sponsors and Collaborators
Women's College Hospital
Canadian Institutes of Health Research (CIHR)
University Health Network, Toronto
NOW Foods
Investigators
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Principal Investigator: An-Wen Chan Women's College Hospital
Principal Investigator: Sang Joseph Kim University Health Network, Toronto
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Responsible Party: Women's College Hospital
ClinicalTrials.gov Identifier: NCT05955924    
Other Study ID Numbers: SPRINTR-pivotal
First Posted: July 21, 2023    Key Record Dates
Last Update Posted: September 26, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Analytic Code

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Basal Cell
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents