Nicotinamide for Non-melanoma Skin Cancer

(SPRINTR Trial)

Recruiting at 7 trial locations

Overseen By Stephanie Jewell, BSc. Hons

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Women's College Hospital

Must be taking: Calcineurin inhibitors

Must not be taking: Nicotinamide, Niacin, Carbamazepine, Primidone

Disqualifiers: Active liver disease, Severe kidney disease, Solid organ malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 208 weeks

396 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have used nicotinamide or niacin in high doses recently, and you cannot be on carbamazepine or primidone. It's best to discuss your current medications with the trial team.

What evidence supports the effectiveness of the drug nicotinamide in reducing non-melanoma skin cancer risk?

Research shows that taking nicotinamide (a form of Vitamin B3) can lower the risk of non-melanoma skin cancers by about 23% in people who have had these types of skin cancers before. It works by helping repair skin damage from the sun and boosting the skin's immune response. ^{1 2 3 4 5}

Is nicotinamide safe for humans?

Nicotinamide (vitamin B3) is generally considered safe for humans, with studies showing it has a favorable side effect profile and is a nontoxic option for reducing the risk of non-melanoma skin cancers. ^{1 2 4 6 7}

How does the drug nicotinamide differ from other treatments for non-melanoma skin cancer?

Nicotinamide (Vitamin B3) is unique because it is taken orally and works by enhancing DNA repair, reducing UV-induced immune suppression, and restoring cellular energy, making it a non-toxic and accessible option for preventing non-melanoma skin cancers, especially in high-risk individuals. ^{1 2 3 4 5}

Research Team

An-Wen Chan

Principal Investigator

Women's College Hospital

Sang Joseph Kim

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adult organ transplant recipients who are on specific immunosuppressants, have had a kidney, liver, heart, or lung transplant over two years ago and have previously had skin cancer. They must be able to attend follow-up visits but can't join if they've used certain vitamins recently, had other cancers or severe organ disease in the last five years, are pregnant or breastfeeding.

Inclusion Criteria

I had a transplant (kidney, liver, heart, or lung) over two years ago.

I can go to all my follow-up appointments.

I am 18 years old or older.

Exclusion Criteria

Pregnancy or lactation

I have had a serious cancer or skin cancer spread in the last 5 years.

I have skin cancer that hasn't been treated yet, but I can join after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral nicotinamide (500 mg twice daily) or placebo for up to 208 weeks

208 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide
• Placebo

Trial Overview The study tests whether Nicotinamide (Vitamin B3) can prevent skin cancer in patients with organ transplants who are at high risk due to their anti-rejection medications. Participants will receive either Nicotinamide or placebo pills twice daily for up to four years across multiple Canadian centers.

Participant Groups

Group I: Nicotinamide Experimental Treatment 1 Intervention

Intervention Drug : Nicotinamide

Group II: Placebo Placebo Group 1 Intervention

Intervention: Placebo Oral Capsule

Nicotinamide is already approved in United States, European Union for the following indications:

Approved in United States as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Approved in European Union as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Who Is Running the Clinical Trial?

Women's College Hospital

Lead Sponsor

Trials

108

Recruited

43,700+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

NOW Foods

Collaborator

Trials

6

Recruited

690+

Findings from Research

In a study of 203 adults with a history of multiple non-melanoma skin cancers, patients were willing to accept a 23% reduction in skin cancer risk with a modest increase in cost, but they were not willing to accept a significant increase in severe infection risk associated with nicotinamide supplementation.

The findings suggest that while nicotinamide can reduce skin cancer risk, the potential for increased severe infections may deter patients from choosing this treatment, indicating a need for careful consideration of patient preferences in treatment recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. Boeri, M., Skelsey, MK., Schiro, JA., et al.[2023]

Nicotinamide (NAM), a form of vitamin B3, has been shown to significantly reduce the incidence of actinic keratoses and non-melanoma skin cancers in a Phase III double-blinded placebo-controlled study involving skin cancer patients.

While NAM is effective in preventing skin cancer, its benefits require continuous supplementation, as the protective effects diminish quickly after stopping intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nicotinamide: The role in skin cancer chemoprevention. Giacalone, S., Spigariolo, CB., Bortoluzzi, P., et al.[2021]

A survey of 50 patients who underwent Mohs surgery revealed that those taking nicotinamide perceived a higher risk reduction for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with reductions of 41.2% and 38.3%, respectively.

Despite a significant perceived benefit, only 15.6% of respondents believed nicotinamide was more effective than sunscreen, highlighting the need for better patient education on the role of nicotinamide in reducing skin cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perception of Skin Cancer Reduction by Nicotinamide Correlates With Use. Schneider, JG., Majidian, M., Moy, RL.[2023]

Nicotinamide (vitamin B3) has demonstrated multiple protective effects against UV damage, including enhancing DNA repair and restoring cellular energy levels, which can help maintain skin health.

In high-risk individuals, pharmacological doses of nicotinamide significantly reduce the incidence of actinic keratoses and nonmelanoma skin cancers, making it a safe and effective option for skin cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide for skin cancer chemoprevention. Damian, DL.[2018]

Oral nicotinamide supplementation has been studied in five randomized controlled trials and other studies, showing a potential benefit in reducing the incidence of non-melanoma skin cancers (NMSC), particularly in high-risk individuals.

While current evidence is not definitive, nicotinamide has a favorable safety profile, making it a low-risk option for managing skin cancer risk, especially for those with a history of skin issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nicotinamide for non-melanoma skin cancers: A review. Hunt, SV., Jamison, A., Malhotra, R.[2023]

A significant majority (76.9%) of Mohs surgeons recommend nicotinamide for preventing keratinocyte carcinoma (KC), indicating its acceptance as a preventive treatment in clinical practice.

Most surgeons (63.8%) have no safety concerns regarding long-term use of nicotinamide, although those with safety concerns and more experienced surgeons (over 10 years in practice) were less likely to recommend it, suggesting a need for further research on its long-term safety and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide for Keratinocyte Carcinoma Chemoprevention: A Nationwide Survey of Mohs Surgeons. Desai, S., Olbricht, S., Ruiz, ES., et al.[2021]

Oral nicotinamide supplementation may help lower the risk of non-melanoma skin cancers, suggesting a potential preventive strategy for at-risk individuals.

Despite the current lack of definitive proof, nicotinamide is considered safe with a favorable side effect profile, making it a viable option for those at higher risk of skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide and Nonmelanoma Skin Cancers. Jamison, A., Malhotra, R.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Oral nicotinamide: The role in skin cancer chemoprevention. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Patient Perception of Skin Cancer Reduction by Nicotinamide Correlates With Use. [2023]

4. Australia pubmed.ncbi.nlm.nih.gov

Nicotinamide for skin cancer chemoprevention. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Oral nicotinamide for non-melanoma skin cancers: A review. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide for Keratinocyte Carcinoma Chemoprevention: A Nationwide Survey of Mohs Surgeons. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide and Nonmelanoma Skin Cancers. [2022]