Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial

NCT03769285 | Unknown Phase 2 DMC

• 1 other identifier: SPRINTR-Pilot
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A common long-term side effect of anti-rejection (immunosuppressant) medications is skin cancer. This pilot clinical trial evaluates the feasibility of conducting a larger pivotal trial to examine the efficacy and safety of nicotinamide for prevention of keratinocyte carcinoma in solid organ transplant recipients. This pilot trial will transition into the pivotal trial if all feasibility targets are met.

Conditions

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

Outcome Measures

Primary Outcomes (9)

• Feasibility (pertaining to patient recruitment)

  Proportion of patients who consent to data linkage to provincial administrative databases

  1 year

• Feasibility (pertaining to appropriateness of eligibility criteria)

  Reasons for exclusion of screened patients

  1 year

• Feasibility (pertaining to adherence to intervention)

  Proportion of capsules returned, reasons for non-adherence

  1 year

• Feasibility (pertaining to adherence to follow-up assessments)

  Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation

  1 year

• Feasibility (pertaining to data linkage)

  Proportion of patients who consent to data linkage to provincial administrative databases

  1 year

• Preliminary pooled keratinocyte carcinoma event rate

  Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.

  1 year

• Drug interactions

  Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 1 week. An increased level will be classified as clinically relevant if the transplant physician reduces the immunosuppressant dose in response to the increased drug level.

  1 week

• Drug interactions

  Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 2 weeks. This measurement will be dropped if all cases of clinically relevant drug interactions manifest at 1 week in the first 20 enrolled participants.

  2 weeks

• Serious adverse events

  Descriptive tabulation (preliminary safety)

  1 year

Secondary Outcomes (9)

• Feasibility of recruiting for neurocognitive substudy

  1 year

• Baseline prevalence of cognitive impairment (substudy)

  1 year

• Pooled standard deviation of MoCA test scores (substudy)

  1 year

• Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)

  1 year

• Pooled standard deviation of Trail Making A and B test scores (substudy)

  1 year

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Drug: Nicotinamide

Placebo

PLACEBO COMPARATOR

Drug: Placebo oral capsule

Interventions

Nicotinamide DRUG

Oral nicotinamide (500 mg) twice daily for at least 52 weeks

Also known as: niacinamide

Nicotinamide

Placebo oral capsule DRUG

Matching placebo taken twice daily for at least 52 weeks

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
• Able to speak and understand English (only for cognitive substudy)

You may not qualify if:

• Use of mTOR inhibitor (sirolimus, everolimus) within the past 12 weeks
• Biopsy-confirmed acute rejection episode within the past 12 weeks
• Active liver disease (elevated AST or ALT \>3 times normal)
• Severe renal failure (estimated glomerular filtration rate \<20 mL/min/1.73 m2)
• Current carbamazepine or primidone use
• Pregnancy and lactation
• Gorlin syndrome or other genetic skin cancer syndrome
• Solid organ or hematologic malignancy, invasive Stage II melanoma, Merkel cell carcinoma, or metastatic skin cancer within the past five years, or invasive Stage I melanoma within the past two years
• Untreated localized skin cancer (invasive squamous cell carcinoma, basal cell carcinoma, or keratoacanthoma) at baseline (the patient can enrol after skin cancer treatment)
• Use of nicotinamide or niacin (250 mg or more daily) within the past 12 weeks
• Use of field therapy for actinic keratoses within the past 12 weeks
• Initiation of systemic chemoprevention within the past 12 weeks

Sponsors & Collaborators

• Women's College Hospital: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• The Kidney Foundation of Canada: collaborator
• NOW Foods: collaborator
• Natural Life Nutrition: collaborator

Study Sites (1)

Toronto General Hospital, University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

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, MD DPhil

  Women's College Hospital

  PRINCIPAL INVESTIGATOR

• Joseph Kim, MD PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: December 7, 2018
• Study Start: December 3, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: 2 years after completion of the pivotal trial that follows this pilot trial

Locations

CA (1)