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

NCT05955924 | Recruiting Phase 3

• 1 other identifier: SPRINTR-pivotal
• Study Type: interventional
• Target: 396
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma)

  Up to 208 weeks

Secondary Outcomes (43)

• 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

  208 weeks

• Acute graft rejection (biopsy-confirmed)

  208 weeks

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Intervention Drug : Nicotinamide

Drug: Nicotinamide

Placebo

PLACEBO COMPARATOR

Intervention: Placebo Oral Capsule

Drug: Placebo

Interventions

Nicotinamide DRUG

Oral nicotinamide (500 mg) twice daily

Also known as: niacinamide

Nicotinamide

Placebo DRUG

Matching placebo capsule twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Women's College Hospital: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• University Health Network, Toronto: collaborator
• NOW Foods: collaborator

Study Sites (7)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

NOT YET RECRUITING

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Carcinoma, Basal Cell

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms, Basal Cell

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• An-Wen Chan

  Women's College Hospital

  PRINCIPAL INVESTIGATOR

• Sang Joseph Kim

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Jewell, BSc. Hons

CONTACT

416 351-3732; sprintr@wchospital.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, parallel group, placebo-controlled, pragmatic randomized trial with 1:1 allocation and a superiority framework

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 21, 2023
• Study Start: August 28, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beyond 18 months after trial completion.
• 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.

Locations

CA (7)