Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
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Description Module
Ignite Creation Date:
2025-12-25 @ 4:59 AM
Ignite Modification Date:
2025-12-25 @ 4:59 AM
NCT ID:
NCT07286318
Brief Summary:
A Randomized Controlled Trial of Topical 5% Niacinamide for Skin Cancer Prevention in Organ Transplant Recipients
This study is designed to evaluate whether a topical 5% niacinamide cream can help prevent skin cancer in organ transplant recipients. Individuals who have received an organ transplant have a much higher risk of developing precancerous skin growths and skin cancers because of long-term immune-suppressing medications. Although sunscreen is an important part of sun protection, additional preventive approaches are needed. Early research suggests that niacinamide may help protect the skin, and this trial will examine whether a topical formulation provides benefit in this high-risk group.
The study will test whether daily use of topical 5% niacinamide reduces the number of actinic keratoses over 6 and 12 months and whether it decreases the development of new keratinocyte cancers when compared with sunscreen alone. The study will also evaluate how well the topical product is tolerated and whether it can be used consistently as part of a daily skin-care routine.
A total of 20 adult organ transplant recipients with a history of multiple actinic keratoses and at least one prior non-melanoma skin cancer will enroll in this 12-month, randomized, controlled trial. Participants will be assigned to receive either daily topical 5% niacinamide plus sunscreen or sunscreen alone. Skin examinations will be performed at 6 and 12 months using standardized mapping methods. Information on treatment tolerability, adherence, and any side effects will be collected through structured surveys, and any lesions suspicious for cancer will be evaluated by a board-certified pathologist.
Detailed Description:
Background, Significance, and Preliminary Studies
Organ transplant recipients (OTRs) have at least a 50 times higher risk of developing non-melanoma skin cancers than the general population (Moloney et al., 2006). These skin cancers in OTRs also tend to be more aggressive, with higher rates of recurrence and metastasis (Martinez et al., 2003). Immunosuppression in OTRs is primarily achieved through the use of pharmacologic agents such as mycophenolate mofetil, azathioprine, cyclosporine, and tacrolimus, among other medications. These agents work by inhibiting various components of the immune system to prevent graft rejection. For instance, calcineurin inhibitors like cyclosporine and tacrolimus inhibit T-cell activation by blocking the production of interleukin-2 (IL-2), a critical cytokine for T-cell proliferation. Mycophenolate mofetil and azathioprine inhibit purine synthesis, thereby reducing lymphocyte proliferation. These immunosuppressive drugs, while effective in preventing rejection, also impair DNA repair mechanisms and immune surveillance and increase the risk of malignancies, particularly skin cancers.
Nicotinamide (NAM), the amide derivative of vitamin B3, has been investigated for its potential role in reducing the incidence of skin cancer. Ultraviolet (UV) radiation exposure in the absence of NAM results in a significant reduction in cellular adenosine triphosphate (ATP) levels. NAM has been shown to enhance DNA repair mechanisms and mitigate UV-induced immunosuppression by preserving cellular ATP levels (Park et al., 2010). In the context of oncogenesis, the maintenance of ATP levels is commonly associated with the promotion of antitumor immune responses, whereas elevated levels of extracellular adenosine (ADO) are often seen in cancer. The ectonucleotidase CD39 catalyzes the rate-limiting step in the hydrolysis of extracellular ATP to extracellular ADO. Work by Whitley et al. (2021), employing a murine model, demonstrated that CD39 expression on skin-resident T cells regulates DNA damage repair through ATP-mediated signaling pathways. Taken together, these findings suggest a mechanistic pathway by which NAM may exert chemopreventive effects. NAM appears to maintain cellular ATP levels, which facilitates DNA repair and supports antitumor immunity through the modulation of extracellular ATP and adenosine (ADO) signaling.
Several other potential mechanisms by which NAM may be chemoprotective are described in the literature. In human keratinocyte cultures, tumor protein p53 (TP53), a key protector of the DNA damage response, was significantly upregulated following UV exposure in the presence of NAM when compared to UV exposure without NAM (Sirapivabu et al., 2009). TP53 is often referred to as the guardian of the genome and its loss is observed in many cancers. Further, keratinocytes treated with NAM and exposed to UV radiation and arsenic demonstrated protection against cyclobutane pyrimidine dimer (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine formation, which are DNA photolesions (Damian et al., 2015). Photolesions can result in carcinogenic mutations if not repaired. NAM has also been shown to facilitate repair of such photolesions through multiple pathways (Surjana et al., 2013).
While oral NAM has shown promise in skin cancer prevention, clinical trials in high-risk patients have yielded mixed results. A phase 3 randomized controlled trial by Chen et al. (2015) of 386 high-risk immunocompetent patients demonstrated that oral nicotinamide (500 mg twice daily for 12 months) significantly reduced the rate of new nonmelanoma skin cancers (NMSCs) by 23% (P = 0.02) compared to placebo. Reductions were observed for new squamous cell carcinomas (30% reduction, P = 0.05) and basal cell carcinomas (20% reduction, P = 0.12), and actinic keratoses counts were significantly lower throughout treatment (P \< 0.001 at multiple time points). A pilot double-blind randomized trial in renal transplant patients by Chen et al. (2016) evaluated oral nicotinamide (500 mg twice daily) for prevention of nonmelanoma skin cancers (NMSCs) and actinic keratoses (AKs). Over 6 months, nicotinamide showed a nonsignificant 35% relative reduction in NMSC rate (P = 0.36) and a 16% reduction in AKs (P = 0.15) compared to placebo. A study by Hwang et al. (2025) utilized a retrospective cohort study design to evaluate the effect of oral nicotinamide supplementation in a group of 47 OTRs. It was demonstrated that nicotinamide 500 mg twice daily for at least a year decreased the incidence of KCs at one and two year follow up (Hwang et al., 2025).
However, the beneficial effects observed in these studies have not been consistent throughout the literature. A recent phase 3 randomized trial by Allen et al. (2023) evaluated oral nicotinamide (vitamin B3) for skin cancer chemoprevention in OTRs. Despite previous promising results in immunocompetent individuals, the study found no significant reduction in new AKs with oral NAM over 12 months compared to placebo (Allen et al., 2023). However, while not statistically significant, a notable trend toward reduced invasive squamous cell carcinoma (SCC) was observed in the NAM treated patients. In addition, this study has significant limitations as it terminated early due to poor recruitment. Another small, randomized trial of 30 patients by Zhang et al. (2023) evaluated oral NAM for preventing AKs in kidney transplant recipients with prior keratinocyte carcinoma. The study found no significant reduction in AK development with oral NAM (500 mg twice daily) over 12 months compared to placebo. Tolerability issues led to dose reduction and higher attrition in the NAM group, highlighting challenges with systemic therapy in this population. These findings underscore the need to investigate alternative and synergistic approaches, such as topical niacinamide, which may improve tolerability and localized efficacy for skin cancer prevention in transplant recipients.
Topical niacinamide offers an exciting alternative and possible adjunct chemopreventive strategy for transplant patients. By directly targeting the skin, sunscreen containing topical niacinamide has been shown to prevent UV-induced immunosuppression by altering multiple pathways similar to the oral form including cell cycle, apoptosis, immunoregulation, and cellular energy (Torres-Moral et al., 2024) Topical niacinamide's excellent safety profile and localized action make it a promising additional or standalone approach for skin cancer chemoprevention in high-risk populations. Further studies would be helpful to explore its full potential in transplant dermatology.
Preliminary studies by our group are evaluating transplant patients' medication preferences and openness to try a product with topical niacinamide to potentially decrease risk for skin cancer. A pilot dataset from our group (n=10) demonstrated that oral medication use is high, with 8/10 participants taking seven or more medications daily. Concerns about oral medications are notable, with 7/10 participants reported being concerned or somewhat concerned about side effects, and 6/10 being concerned or somewhat concerned with drug interactions. Use of topical medications is less prevalent, with 8/10 participants using 0-1 per day and there were fewer concerns with interactions and side effects. When informed about the potential skin cancer prevention benefits of topical niacinamide, 7/10 participants reported that they would be very or somewhat likely to try this in their daily routine. The key factor influencing willingness to try such a product was recommendation from a healthcare provider, selected by 9/10 patients. Overall, these results support further studies of topical niacinamide in transplant patients given the high prevalence of polypharmacy, concerns with oral medications, and willingness to try a new topical product if recommended from their health care provider.
Experimental Design
Study Design
Type: Prospective, randomized, controlled trial
Duration: 12 months
Participants: 20 OTRs with history of ≥5 AKs in the past two years and ≥1 prior NMSC Materials: 5% topical niacinamide in a vanicream base will be purchased from The Burgh Pharmacy and provided to participants. No other active ingredients will be added.
Randomization: 1:1 into two arms:
Arm A (Intervention): Topical 5% niacinamide cream applied once daily + SPF 30 sunscreen daily and every 2 hours when outdoors.
Arm B (Control): SPF 30 sunscreen daily and every 2 hours when outdoors. Inclusion Criteria: Age ≥18; History of solid organ transplantation; At least 5 AKs in the past year and prior history of non-melanoma skin cancer Exclusion Criteria: Known allergy to niacinamide or sunscreen components Outcome Measures
Primary Outcome:
Change in AK count at 6 and 12 months, measured by standardized assessment and clinical quantification (see below)
Secondary Outcomes:
Incidence of new keratinocyte carcinomas, confirmed by a board-certified pathologist from histological evaluation Tolerability and adverse events Patient adherence and experience; this will be analyzed using a RedCap survey at the end of the study Quantification: Actinic keratoses and non-melanoma skin cancers will be quantified at regular 6 and 12-month follow-up visits using a standardized scale and transparent sheet for record keeping.
This will be performed using previously published methods by Jansen and Olsen (see below). The severity of each actinic keratosis will be graded with the Olsen scale: 1=mild, 2=moderate or 3=severe. In this classification system, lesions are graded as Olsen Grade I when they are slightly palpable and more easily felt than seen; as Olsen Grade II when the lesions are moderately thick and easy to see and feel; and graded as Olsen Grade III when the lesions are very thick hyperkeratotic AK.
Data Analysis Plan: Comparative analyses of clinical outcomes will be conducted to evaluate the efficacy of the intervention. Differences in actinic keratosis (AK) counts between study arms will be analyzed using two-sample t-tests, and comparisons of incident non-melanoma skin cancer (NMSC) counts will likewise be performed using t-tests, using paired and unpaired approaches. Quantitative findings will be visualized through appropriately scaled bar charts, line graphs, and heat maps to facilitate interpretation of between-group differences. Patient-reported outcomes will include both structured survey responses and open-ended questions. Quantitative survey responses will be analyzed using standard statistical methods, while qualitative responses will undergo systematic content analysis to identify salient themes and patient perspectives.
Study:
NCT07286318
Study Brief:
Protocol Section:
NCT07286318