Trial Title:
Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients - Pivotal Trial
NCT ID:
NCT05955924
Condition:
Non-melanoma Skin Cancer
Carcinoma, Squamous Cell
Carcinoma, Basal Cell
Keratinocyte Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Basal Cell
Niacinamide
Niacin
Nicotinic Acids
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
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
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Matching placebo
Intervention:
Intervention type:
Drug
Intervention name:
Nicotinamide
Description:
Oral nicotinamide (500 mg) twice daily
Arm group label:
Nicotinamide
Other name:
niacinamide
Intervention type:
Drug
Intervention name:
Placebo
Description:
Matching placebo capsule twice daily
Arm group label:
Placebo
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.
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.
Criteria for eligibility:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Calgary
Address:
City:
Calgary
Zip:
T2N 1N4
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
University of Alberta
Address:
City:
Edmonton
Zip:
T6G 2R3
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Vancouver General Hospital
Address:
City:
Vancouver
Zip:
V5Z 1M9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Natalie Ng
Email:
natalie.ng@ubc.ca
Facility:
Name:
St. Paul's Hospital
Address:
City:
Vancouver
Zip:
V6Z 1Y6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Anushka Sood
Email:
asood1@providencehealth.bc.ca
Investigator:
Last name:
John Gill
Email:
Principal Investigator
Investigator:
Last name:
Sheila Au
Email:
Sub-Investigator
Facility:
Name:
The Ottawa Hospital
Address:
City:
Ottawa
Zip:
K1Y 4E9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Christine Lennox
Email:
clennox@ohri.ca
Investigator:
Last name:
Jennifer Beecker
Email:
Principal Investigator
Facility:
Name:
Toronto General Hospital
Address:
City:
Toronto
Zip:
M5G 2C4
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Marsida Stafa
Email:
SPRINTR@wchospital.ca
Investigator:
Last name:
An-Wen Chan
Email:
Principal Investigator
Facility:
Name:
Women's College Hospital
Address:
City:
Toronto
Zip:
M5S 1B2
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Nihil Dobariya
Email:
SPRINTR@wchospital.ca
Investigator:
Last name:
An-Wen Chan
Email:
Principal Investigator
Start date:
August 28, 2023
Completion date:
August 2027
Lead sponsor:
Agency:
Women's College Hospital
Agency class:
Other
Collaborator:
Agency:
Canadian Institutes of Health Research (CIHR)
Agency class:
Other
Collaborator:
Agency:
University Health Network, Toronto
Agency class:
Other
Collaborator:
Agency:
NOW Foods
Agency class:
Other
Source:
Women's College Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05955924
