Nicotinamide for Prevention of Pre-malignant Actinic Keratosis in Kidney Transplant Recipients

NCT04843553 | Completed Early Phase 1

• 1 other identifier: Rhode islandHospital
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Skin cancers and pre-cancerous growths (called actinic keratoses, "AKs"), that aren't melanomas, develop in patients with a kidney transplant at excessive rates. When these pre-cancerous AKs, and "non-melanoma" skin cancers occur in kidney transplant patients, they tend to be aggressive, and require frequent medical procedures, often surgery, for the removal of the skin cancers. If not removed adequately the pre-cancers can develop into skin cancers, and the skin cancers, if not removed, may spread, and even cause death. Reducing the occurrence and complications of these skin cancers and pre-cancers in kidney transplant patients with a safe, effective, well-tolerated treatment taken by mouth would be an important medical advance. We are testing oral nicotinamide (NAM)-a B-vitamin compound-for that purpose. Approximately fifty kidney transplant patients who have had at least one non-melanoma skin cancer in the past, will be given randomized to receive NAM, 1 gram twice daily by mouth, or identical pills without NAM, and followed for 1 year to see if NAM treatment reduces the numbers of pre-cancerous AKs, and non-melanoma skin cancers they develop. Patients will be asked to come to the clinic for 3 follow up visits (every 4 months for up to 12 months). They will receive a full body skin exam by a dermatologist, have detailed counting of AKs and biopsies for any suspicious lesions as standard of care. Blood will also be drawn as well as a urine sample obtained at each visit for safety assessment and storage. We will also ask them to answer a series of questions about dietary patterns and intake of whole foods and supplements.

Conditions

Actinic Keratoses

Keywords

Nicotinamide, AKs

Outcome Measures

Primary Outcomes (1)

• Effects of oral nicotinamide on AKs

  To evaluate the effects of oral nicotinamide 1gram/day, given in two divided doses, for 9- 12-months, versus matched placebo, on the total number of actinic keratoses which develop in stable chronic kidney transplant recipients with a history of at least one non-melanoma skin cancer (keratinocyte carcinoma). To evaluate the effects of oral nicotinamide 1gram/day, given in two divided doses, for 9- 12-months, versus matched placebo, on the total number of actinic keratoses which develop in stable chronic kidney transplant recipients with a history of at least one non-melanoma skin cancer (keratinocyte carcinoma).

  12 months

Study Arms (2)

active

ACTIVE COMPARATOR

Participants receiving oral vitamin B-3

Drug: Oral Nicotinamide

placebo

PLACEBO COMPARATOR

Participants receiving oral inactive pill

Drug: Oral Nicotinamide

Interventions

Oral Nicotinamide DRUG

Also known as: Vitamin B-3

active; placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplant ≥ 12-months ago
• ongoing, standard immunosuppression regimen
• current CKD
• EPI estimated (43)
• glomerular filtration rate (eGFR) ≥ 15 ml/min per 1.73 m2)
• Prior history of at least one NMSC

You may not qualify if:

• Kidney transplant \<12-months ago, treatment for acute rejection \<= 3-months ago, or current eGFR\< 20
• Known history of active liver disease/ transaminitis \[alanine aminotransferase, ALT \> 1.5 X upper limit of normal\]
• Serum phosphorus \< 2.0 mg/dL or average ≤ 100 × 10(9)/mL platelets
• Internal malignancy, metastatic SCC, or invasive melanoma within the past 5-years
• Overwhelming numbers of current skin cancers or large areas of confluent skin cancer at baseline preventing accurate assessment and counting of new skin cancers
• Field treatment for AKs within the past 4-weeks, preventing accurate assessment of AKs
• Patients begun on acitretin or other oral retinoids, or mTOR inhibitors within the past 6-months (If stably taking for more than six months, they may participate)
• Gorlin's syndrome or other genetic skin cancer syndrome
• Patients unavailable for follow-up for the duration of the study because of social/ geographical reasons, or general frailty
• Pregnancy or lactation (all women of childbearing will be required to use contraception throughout the study)
• Patients taking supplemental NAM within the past 4-weeks

Sponsors & Collaborators

• Rhode Island Hospital: lead

Related Publications (3)

• Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol. 2015 Oct;151(10):1081-6. doi: 10.1001/jamadermatol.2015.1187.

  PMID: 25928283 BACKGROUND

• Hartevelt MM, Bavinck JN, Kootte AM, Vermeer BJ, Vandenbroucke JP. Incidence of skin cancer after renal transplantation in The Netherlands. Transplantation. 1990 Mar;49(3):506-9. doi: 10.1097/00007890-199003000-00006.

  PMID: 2316011 BACKGROUND

• Webb MC, Compton F, Andrews PA, Koffman CG. Skin tumours posttransplantation: a retrospective analysis of 28 years' experience at a single centre. Transplant Proc. 1997 Feb-Mar;29(1-2):828-30. doi: 10.1016/s0041-1345(96)00152-2. No abstract available.

  PMID: 9123544 BACKGROUND

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Niacinamide; Niacin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Reginald m Gohh

  Rhode Island Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Research Pharmacists used list provided by biostatistician to fill unidentified (except for patient name) pill bottles.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2021
• First Posted: April 13, 2021
• Study Start: October 14, 2016
• Primary Completion: February 8, 2019
• Study Completion: December 18, 2020
• Last Updated: April 22, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share