<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03769285</url>
  </required_header>
  <id_info>
    <org_study_id>SPRINTR-Pilot</org_study_id>
    <nct_id>NCT03769285</nct_id>
  </id_info>
  <brief_title>Skin Cancer Prevention With Nicotinamide in Transplant Recipients - Pilot Trial</brief_title>
  <acronym>SPRINTR-Pilot</acronym>
  <official_title>Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: A Pilot, Placebo-controlled, Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Women's College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Kidney Foundation of Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NOW Foods</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Natural Life Nutrition</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Women's College Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A common long-term side effect of anti-rejection (immunosuppressant) medications is skin&#xD;
      cancer. This pilot clinical trial evaluates the feasibility of conducting a larger pivotal&#xD;
      trial to examine the efficacy and safety of nicotinamide for prevention of keratinocyte&#xD;
      carcinoma in solid organ transplant recipients. This pilot trial will transition into the&#xD;
      pivotal trial if all feasibility targets are met.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility (pertaining to patient recruitment)</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of patients who consent to data linkage to provincial administrative databases</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility (pertaining to appropriateness of eligibility criteria)</measure>
    <time_frame>1 year</time_frame>
    <description>Reasons for exclusion of screened patients</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility (pertaining to adherence to intervention)</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of capsules returned, reasons for non-adherence</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility (pertaining to adherence to follow-up assessments)</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility (pertaining to data linkage)</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of patients who consent to data linkage to provincial administrative databases</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preliminary pooled keratinocyte carcinoma event rate</measure>
    <time_frame>1 year</time_frame>
    <description>Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug interactions</measure>
    <time_frame>1 week</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug interactions</measure>
    <time_frame>2 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Descriptive tabulation (preliminary safety)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility of recruiting for neurocognitive substudy</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of enrolled participants who consent to participate in the neurocognitive substudy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline prevalence of cognitive impairment (substudy)</measure>
    <time_frame>1 year</time_frame>
    <description>Montreal Cognitive Assessment (MoCA) score &lt;26, scored out of 30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of MoCA test scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <description>Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <description>Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of Trail Making A and B test scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of Controlled Oral Word Association test scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of Animal Naming Task scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of cognitive test scores (substudy)</measure>
    <time_frame>1 year</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pooled standard deviation of serum phosphate levels (substudy)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Non-melanoma Skin Cancer</condition>
  <condition>Carcinoma, Squamous Cell</condition>
  <condition>Carcinoma, Basal Cell</condition>
  <arm_group>
    <arm_group_label>Nicotinamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotinamide</intervention_name>
    <description>Oral nicotinamide (500 mg) twice daily for at least 52 weeks</description>
    <arm_group_label>Nicotinamide</arm_group_label>
    <other_name>niacinamide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Matching placebo taken twice daily for at least 52 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years old&#xD;
&#xD;
          2. Kidney, liver, heart, or lung transplant at least two years ago&#xD;
&#xD;
          3. History of at least one prior histologically-confirmed keratinocyte carcinoma or&#xD;
             squamous cell carcinoma in situ&#xD;
&#xD;
          4. Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or&#xD;
             tacrolimus)&#xD;
&#xD;
          5. Able to attend follow-up visits&#xD;
&#xD;
          6. Able to speak and understand English (only for cognitive substudy)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of mTOR inhibitor (sirolimus, everolimus) within the past 12 weeks&#xD;
&#xD;
          2. Biopsy-confirmed acute rejection episode within the past 12 weeks&#xD;
&#xD;
          3. Active liver disease (elevated AST or ALT &gt;3 times normal)&#xD;
&#xD;
          4. Severe renal failure (estimated glomerular filtration rate &lt;20 mL/min/1.73 m2)&#xD;
&#xD;
          5. Current carbamazepine or primidone use&#xD;
&#xD;
          6. Pregnancy and lactation&#xD;
&#xD;
          7. Gorlin syndrome or other genetic skin cancer syndrome&#xD;
&#xD;
          8. Solid organ or hematologic malignancy, invasive Stage II melanoma, Merkel cell&#xD;
             carcinoma, or metastatic skin cancer within the past five years, or invasive Stage I&#xD;
             melanoma within the past two years&#xD;
&#xD;
          9. Untreated localized skin cancer (invasive squamous cell carcinoma, basal cell&#xD;
             carcinoma, or keratoacanthoma) at baseline (the patient can enrol after skin cancer&#xD;
             treatment)&#xD;
&#xD;
         10. Use of nicotinamide or niacin (250 mg or more daily) within the past 12 weeks&#xD;
&#xD;
         11. Use of field therapy for actinic keratoses within the past 12 weeks&#xD;
&#xD;
         12. Initiation of systemic chemoprevention within the past 12 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>An-Wen Chan, MD DPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Women's College Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joseph Kim, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network, Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toronto General Hospital, University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Basal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niacinamide</mesh_term>
    <mesh_term>Niacin</mesh_term>
    <mesh_term>Nicotinic Acids</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>2 years after completion of the pivotal trial that follows this pilot trial</ipd_time_frame>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03769285
org study id: SPRINTR-Pilot
nct id: NCT03769285
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Feasibility (pertaining to patient recruitment)
time frame: 1 year
description: Proportion of patients who consent to data linkage to provincial administrative databases
measure: Feasibility (pertaining to appropriateness of eligibility criteria)
time frame: 1 year
description: Reasons for exclusion of screened patients
measure: Feasibility (pertaining to adherence to intervention)
time frame: 1 year
description: Proportion of capsules returned, reasons for non-adherence
measure: Feasibility (pertaining to adherence to follow-up assessments)
time frame: 1 year
description: Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation
measure: Feasibility (pertaining to data linkage)
time frame: 1 year
description: Proportion of patients who consent to data linkage to provincial administrative databases
measure: Preliminary pooled keratinocyte carcinoma event rate
time frame: 1 year
description: Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.
measure: Drug interactions
time frame: 1 week
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.
measure: Drug interactions
time frame: 2 weeks
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.
measure: Serious adverse events
time frame: 1 year
description: Descriptive tabulation (preliminary safety)
measure: Feasibility of recruiting for neurocognitive substudy
time frame: 1 year
description: Proportion of enrolled participants who consent to participate in the neurocognitive substudy
measure: Baseline prevalence of cognitive impairment (substudy)
time frame: 1 year
description: Montreal Cognitive Assessment (MoCA) score <26, scored out of 30.
measure: Pooled standard deviation of MoCA test scores (substudy)
time frame: 1 year
description: Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function
measure: Pooled standard deviation of Hopkins Verbal Learning Test - Revised scores (substudy)
time frame: 1 year
description: Hopkins Verbal Learning Test - Revised, a memory test scored out of 60, with a higher score representing better memory
measure: Pooled standard deviation of Trail Making A and B test scores (substudy)
time frame: 1 year
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
measure: Pooled standard deviation of Controlled Oral Word Association test scores (substudy)
time frame: 1 year
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.
measure: Pooled standard deviation of Animal Naming Task scores (substudy)
time frame: 1 year
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
measure: Pooled standard deviation of cognitive test scores (substudy)
time frame: 1 year
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
measure: Pooled standard deviation of serum phosphate levels (substudy)
time frame: 1 year
arm group label: Nicotinamide
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Nicotinamide
description: Oral nicotinamide (500 mg) twice daily for at least 52 weeks
arm group label: Nicotinamide
other name: niacinamide
intervention type: Drug
intervention name: Placebo oral capsule
description: Matching placebo taken twice daily for at least 52 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: An-Wen Chan, MD DPhil
role: Principal Investigator
affiliation: Women's College Hospital
last name: Joseph Kim, MD PhD
role: Principal Investigator
affiliation: University Health Network, Toronto
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Skin Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Carcinoma, Basal Cell
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Analytic Code
ipd time frame: 2 years after completion of the pivotal trial that follows this pilot trial