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Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial (SPRINTR-Pilot)

Primary Purpose

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

Status
Active
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Nicotinamide
Placebo oral capsule
Sponsored by
Women's College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Non-melanoma Skin Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. Kidney, liver, heart, or lung transplant at least two years ago
  3. History of at least one prior histologically-confirmed keratinocyte carcinoma or squamous cell carcinoma in situ
  4. Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or tacrolimus)
  5. Able to attend follow-up visits
  6. Able to speak and understand English (only for cognitive substudy)

Exclusion Criteria:

  1. Use of mTOR inhibitor (sirolimus, everolimus) within the past 12 weeks
  2. Biopsy-confirmed acute rejection episode within the past 12 weeks
  3. Active liver disease (elevated AST or ALT >3 times normal)
  4. Severe renal failure (estimated glomerular filtration rate <20 mL/min/1.73 m2)
  5. Current carbamazepine or primidone use
  6. Pregnancy and lactation
  7. Gorlin syndrome or other genetic skin cancer syndrome
  8. 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
  9. Untreated localized skin cancer (invasive squamous cell carcinoma, basal cell carcinoma, or keratoacanthoma) at baseline (the patient can enrol after skin cancer treatment)
  10. Use of nicotinamide or niacin (250 mg or more daily) within the past 12 weeks
  11. Use of field therapy for actinic keratoses within the past 12 weeks
  12. Initiation of systemic chemoprevention within the past 12 weeks

Sites / Locations

  • Toronto General Hospital, University Health Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nicotinamide

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Feasibility (pertaining to patient recruitment)
Proportion of patients who consent to data linkage to provincial administrative databases
Feasibility (pertaining to appropriateness of eligibility criteria)
Reasons for exclusion of screened patients
Feasibility (pertaining to adherence to intervention)
Proportion of capsules returned, reasons for non-adherence
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
Feasibility (pertaining to data linkage)
Proportion of patients who consent to data linkage to provincial administrative databases
Preliminary pooled keratinocyte carcinoma event rate
Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.
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.
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.
Serious adverse events
Descriptive tabulation (preliminary safety)

Secondary Outcome Measures

Feasibility of recruiting for neurocognitive substudy
Proportion of enrolled participants who consent to participate in the neurocognitive substudy
Baseline prevalence of cognitive impairment (substudy)
Montreal Cognitive Assessment (MoCA) score <26, scored out of 30.
Pooled standard deviation of MoCA test scores (substudy)
Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function
Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)
Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory
Pooled standard deviation of Trail Making A and B test scores (substudy)
Trail Making A and B, a visual attention test. This records the time (in seconds) to completion, with a faster time representing better cognitive function
Pooled standard deviation of Controlled Oral Word Association test scores (substudy)
Controlled Oral Word Association, a verbal fluency test, measures the production of words belonging to the same letter. This records total number of words produced, with a higher number representing better verbal fluency.
Pooled standard deviation of Animal Naming Task scores (substudy)
Animal Naming Task, a verbal fluency task, measures the total number of animals named in one minute, with a higher number representing better verbal fluency
Pooled standard deviation of cognitive test scores (substudy)
Wechsler Adult Intelligence Scale - Revised, Digit Span subtest, a number sequencing memory test, measures the number of correctly repeated sequences with maximum score of 48. The higher score represents better cognitive function
Pooled standard deviation of serum phosphate levels (substudy)

Full Information

First Posted
December 4, 2018
Last Updated
April 4, 2023
Sponsor
Women's College Hospital
Collaborators
Canadian Institutes of Health Research (CIHR), The Kidney Foundation of Canada, NOW Foods, Natural Life Nutrition
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1. Study Identification

Unique Protocol Identification Number
NCT03769285
Brief Title
Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial
Acronym
SPRINTR-Pilot
Official Title
Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: A Pilot, Placebo-controlled, Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 3, 2018 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Women's College Hospital
Collaborators
Canadian Institutes of Health Research (CIHR), The Kidney Foundation of Canada, NOW Foods, Natural Life Nutrition

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-melanoma Skin Cancer, Carcinoma, Squamous Cell, Carcinoma, Basal Cell

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nicotinamide
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Nicotinamide
Other Intervention Name(s)
niacinamide
Intervention Description
Oral nicotinamide (500 mg) twice daily for at least 52 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Matching placebo taken twice daily for at least 52 weeks
Primary Outcome Measure Information:
Title
Feasibility (pertaining to patient recruitment)
Description
Proportion of patients who consent to data linkage to provincial administrative databases
Time Frame
1 year
Title
Feasibility (pertaining to appropriateness of eligibility criteria)
Description
Reasons for exclusion of screened patients
Time Frame
1 year
Title
Feasibility (pertaining to adherence to intervention)
Description
Proportion of capsules returned, reasons for non-adherence
Time Frame
1 year
Title
Feasibility (pertaining to adherence to follow-up assessments)
Description
Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation
Time Frame
1 year
Title
Feasibility (pertaining to data linkage)
Description
Proportion of patients who consent to data linkage to provincial administrative databases
Time Frame
1 year
Title
Preliminary pooled keratinocyte carcinoma event rate
Description
Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.
Time Frame
1 year
Title
Drug interactions
Description
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.
Time Frame
1 week
Title
Drug interactions
Description
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.
Time Frame
2 weeks
Title
Serious adverse events
Description
Descriptive tabulation (preliminary safety)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Feasibility of recruiting for neurocognitive substudy
Description
Proportion of enrolled participants who consent to participate in the neurocognitive substudy
Time Frame
1 year
Title
Baseline prevalence of cognitive impairment (substudy)
Description
Montreal Cognitive Assessment (MoCA) score <26, scored out of 30.
Time Frame
1 year
Title
Pooled standard deviation of MoCA test scores (substudy)
Description
Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function
Time Frame
1 year
Title
Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)
Description
Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory
Time Frame
1 year
Title
Pooled standard deviation of Trail Making A and B test scores (substudy)
Description
Trail Making A and B, a visual attention test. This records the time (in seconds) to completion, with a faster time representing better cognitive function
Time Frame
1 year
Title
Pooled standard deviation of Controlled Oral Word Association test scores (substudy)
Description
Controlled Oral Word Association, a verbal fluency test, measures the production of words belonging to the same letter. This records total number of words produced, with a higher number representing better verbal fluency.
Time Frame
1 year
Title
Pooled standard deviation of Animal Naming Task scores (substudy)
Description
Animal Naming Task, a verbal fluency task, measures the total number of animals named in one minute, with a higher number representing better verbal fluency
Time Frame
1 year
Title
Pooled standard deviation of cognitive test scores (substudy)
Description
Wechsler Adult Intelligence Scale - Revised, Digit Span subtest, a number sequencing memory test, measures the number of correctly repeated sequences with maximum score of 48. The higher score represents better cognitive function
Time Frame
1 year
Title
Pooled standard deviation of serum phosphate levels (substudy)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 Able to speak and understand English (only for cognitive substudy) Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
An-Wen Chan, MD DPhil
Organizational Affiliation
Women's College Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph Kim, MD PhD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto General Hospital, University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
If feasibility thresholds are met, this pilot trial will proceed to a larger pivotal trial. The study protocol for the pivotal trial will be published prior to completion of data collection. Beyond 2 years after completion of the pivotal trial, the cleaned, anonymized, participant-level dataset and statistical code will made available for sharing with external researchers upon approval of a study proposal describing the intended data usage.
IPD Sharing Time Frame
2 years after completion of the pivotal trial that follows this pilot trial

Learn more about this trial

Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial

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