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

NCT ID: NCT05955924

Last Updated: 2025-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

396 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-28

Study Completion Date

2027-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-melanoma Skin Cancer Carcinoma, Squamous Cell Carcinoma, Basal Cell Keratinocyte Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicentre, parallel group, placebo-controlled, pragmatic randomized trial with 1:1 allocation and a superiority framework
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Matching placebo

Study Groups

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Nicotinamide

Intervention Drug : Nicotinamide

Group Type EXPERIMENTAL

Nicotinamide

Intervention Type DRUG

Oral nicotinamide (500 mg) twice daily

Placebo

Intervention: Placebo Oral Capsule

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo capsule twice daily

Interventions

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Nicotinamide

Oral nicotinamide (500 mg) twice daily

Intervention Type DRUG

Placebo

Matching placebo capsule twice daily

Intervention Type DRUG

Other Intervention Names

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niacinamide

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role collaborator

NOW Foods

OTHER

Sponsor Role collaborator

Women's College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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An-Wen Chan

Role: PRINCIPAL_INVESTIGATOR

Women's College Hospital

Sang Joseph Kim

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status NOT_YET_RECRUITING

University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status RECRUITING

Toronto General Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Women's College Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Stephanie Jewell, BSc. Hons

Role: CONTACT

416 351-3732 ext. 2706

Facility Contacts

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Coralea Bignell

Role: primary

Kelly Kim

Role: primary

Natalie Ng

Role: primary

Anushka Sood

Role: primary

Christine Lennox

Role: primary

Marsida Stafa

Role: primary

Stephanie Jewell

Role: primary

Other Identifiers

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SPRINTR-pivotal

Identifier Type: -

Identifier Source: org_study_id

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