<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/NCT03042286</url>
  </required_header>
  <id_info>
    <org_study_id>2014/00856</org_study_id>
    <nct_id>NCT03042286</nct_id>
  </id_info>
  <brief_title>SAPhIRE Statin Adverse Drug Reaction</brief_title>
  <acronym>STATIN</acronym>
  <official_title>Study of Pharmacogenomic and Pharmacokinetic Risk Factors Associated With Statin Induced Muscle ADRs (Adverse Drug Reactions) in Singapore Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart Centre Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Heart Centre Singapore</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To find out the pharmacokinetic and genetic risk factors involved in muscular side effects&#xD;
      (myalgia) associated with statin therapy. To learn better ways of identifying risk factors&#xD;
      associated with muscle side effects during statin therapy. To perform laboratory analysis to&#xD;
      identify factors predicting future outcomes. The genetic material, in combination with other&#xD;
      medical information and blood tests, will be available to researchers studying genetic and&#xD;
      other factors that contribute to myalgia caused in some patient population on statin&#xD;
      medication.&#xD;
&#xD;
      Patients on statin are selected for this study. This study will recruit 1500 subjects from&#xD;
      National heart Centre Singapore over a period of 2.5 years.&#xD;
&#xD;
      Participation in the full study includes the donation of genetic material. However, subjects&#xD;
      have the option of not having blood subjected to genetic analysis and still participate in&#xD;
      the study. In this case, blood samples will only be analyzed for the statin drug content.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective is to characterize the relationship between genetic polymorphisms and&#xD;
      inter-individual variability in plasma statin and metabolite concentration(s) and to quantify&#xD;
      its contribution towards clinically significant statin induced muscle ADR phenotypes myopathy&#xD;
      and/or myalgia in Singapore population. Methodology: This research involves the study of two&#xD;
      different kinds of muscle ADRs commonly associated with statin therapy, namely myalgia and&#xD;
      myopathy. The study of myalgia will include the recruitment and sample collection (blood)from&#xD;
      3000 subjects from the outpatient clinic at NUH and NHC, who are on either simvastatin or&#xD;
      atorvastatin. To identify genetic variants associated with altered stain exposure,&#xD;
      investigators will perform an analysis of the drug and metabolite levels in plasma, followed&#xD;
      by a genetic analysis of DNA from the blood samples of the recruited subjects. A subgroup of&#xD;
      30 subjects (15 from NUH and 15 from NHC) from this large cohort will be used to study&#xD;
      intra-subject variability in statin drug and metabolite exposure. The genetic association&#xD;
      analysis of genotype and statin blood measurements will be done using liner regression&#xD;
      analysis. To test the hypothesis that related pharmacokinetic variants are associated with&#xD;
      myalgia and myopathy, investigators will perform the case-control association analysis using&#xD;
      logistic regression to examine the frequency of genetic variant in patients with clinically&#xD;
      identified ADRs and compare it to control subjects without any ADRs. A separate cohort of 200&#xD;
      subjects will be recruited for the myopathy study through the NUH outpatient clinic following&#xD;
      subject identification through an IRB approved medical records review of patients who&#xD;
      were/are any statin drug/dose. Blood samples collected from these patients will be subjected&#xD;
      to genetic analysis to identify genetic variants associated with symptomatic phenotypes.&#xD;
&#xD;
      Potential Benefits and risks: The potential benefits of this study include, identifying&#xD;
      strong risk factors of statin induced muscle symptoms myalgia/myopathy that should inform&#xD;
      clinical practice in minimizing/ managing severity of statin associated muscle symptoms, by&#xD;
      identifying patient populations with an increased risk to statin induced myalgia and/or&#xD;
      myopathy. This information might ultimately inform treatment decisions including drug&#xD;
      selection and dosing and improved prediction of treatment response in a heterogeneous&#xD;
      population. The only possible risk in the study is that associated with blood-taking.&#xD;
      Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle&#xD;
      stick. Fainting sometimes occurs and infection rarely occurs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2015</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">January 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Statin drug and metabolite measurement</measure>
    <time_frame>3 to 6 hours</time_frame>
    <description>Multiple reaction monitoring via a triple quadropole mass spectrometry (MS) platform</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacogenomics associated with statin</measure>
    <time_frame>3 to 6 hours</time_frame>
    <description>DNA extraction will be performed at GIS using Qiagen QIAamp DNA Blood Maxi kit and will be quantified by pico-green serial dilution assays</description>
  </secondary_outcome>
  <enrollment type="Anticipated">1500</enrollment>
  <condition>Myopathy</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      For patients who are sensitive about having genetic material collected, investigators will&#xD;
      provide the option of not having their DNA analyzed in the informed consent form.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Inpatient and outpatient clinics&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For myopathy cohort:&#xD;
&#xD;
               1. Subjects are/were on any statin drugs at any dose&#xD;
&#xD;
               2. Subjects reported/ diagnosed with myopathy =10X normal CK levels&#xD;
&#xD;
               3. Myopathy in subjects were statin induced&#xD;
&#xD;
        For myalgia cohort:&#xD;
&#xD;
          1. Subjects are on either Simvastatin or Atorvastatin&#xD;
&#xD;
          2. If subject experience muscle symptoms without CK elevation (myalgia), it should be&#xD;
             statin induced&#xD;
&#xD;
          3. Compliance to five consecutive statin doses prior to sample collection&#xD;
&#xD;
        For the myalgia subgroup (n=30) for intra-individual variability assessment:&#xD;
&#xD;
          1. Subjects are on either Simvastatin or Atorvastatin&#xD;
&#xD;
          2. If subject experience muscle symptoms without CK elevation (myalgia), it should be&#xD;
             statin induced&#xD;
&#xD;
          3. Subjects are willing to provide two blood samples during each of the 3 separate visits&#xD;
&#xD;
          4. Compliance to five consecutive statin doses prior to sample collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Unable or unwilling to give written informed consent 2. Subjects who are pregnant&#xD;
             or breast feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr Wei Chieh Jack Tan</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Heart Centre Singapore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dr Wei Chieh Jack Tan</last_name>
    <phone>67048892</phone>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Katherina Oh</last_name>
    <phone>67042290</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Heart Centre Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169609</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Wei Chieh Jack Tan</last_name>
      <phone>67048892</phone>
    </contact>
    <contact_backup>
      <last_name>Katherina Oh</last_name>
      <phone>67042290</phone>
    </contact_backup>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>June 14, 2016</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>October 17, 2018</last_update_submitted>
  <last_update_submitted_qc>October 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>statin</keyword>
  <keyword>myalgia</keyword>
  <keyword>myopathy</keyword>
  <keyword>adverse drug reactions (ADRs)</keyword>
  <keyword>pharmacokinetics and pharmacogenetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Diseases</mesh_term>
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03042286
org study id: 2014/00856
nct id: NCT03042286
lead sponsor: 
collaborator: 
has dmc: No
To find out the pharmacokinetic and genetic risk factors involved in muscular side effects
      (myalgia) associated with statin therapy. To learn better ways of identifying risk factors
      associated with muscle side effects during statin therapy. To perform laboratory analysis to
      identify factors predicting future outcomes. The genetic material, in combination with other
      medical information and blood tests, will be available to researchers studying genetic and
      other factors that contribute to myalgia caused in some patient population on statin
      medication.

      Patients on statin are selected for this study. This study will recruit 1500 subjects from
      National heart Centre Singapore over a period of 2.5 years.

      Participation in the full study includes the donation of genetic material. However, subjects
      have the option of not having blood subjected to genetic analysis and still participate in
      the study. In this case, blood samples will only be analyzed for the statin drug content.
Objective is to characterize the relationship between genetic polymorphisms and
      inter-individual variability in plasma statin and metabolite concentration(s) and to quantify
      its contribution towards clinically significant statin induced muscle ADR phenotypes myopathy
      and/or myalgia in Singapore population. Methodology: This research involves the study of two
      different kinds of muscle ADRs commonly associated with statin therapy, namely myalgia and
      myopathy. The study of myalgia will include the recruitment and sample collection (blood)from
      3000 subjects from the outpatient clinic at NUH and NHC, who are on either simvastatin or
      atorvastatin. To identify genetic variants associated with altered stain exposure,
      investigators will perform an analysis of the drug and metabolite levels in plasma, followed
      by a genetic analysis of DNA from the blood samples of the recruited subjects. A subgroup of
      30 subjects (15 from NUH and 15 from NHC) from this large cohort will be used to study
      intra-subject variability in statin drug and metabolite exposure. The genetic association
      analysis of genotype and statin blood measurements will be done using liner regression
      analysis. To test the hypothesis that related pharmacokinetic variants are associated with
      myalgia and myopathy, investigators will perform the case-control association analysis using
      logistic regression to examine the frequency of genetic variant in patients with clinically
      identified ADRs and compare it to control subjects without any ADRs. A separate cohort of 200
      subjects will be recruited for the myopathy study through the NUH outpatient clinic following
      subject identification through an IRB approved medical records review of patients who
      were/are any statin drug/dose. Blood samples collected from these patients will be subjected
      to genetic analysis to identify genetic variants associated with symptomatic phenotypes.

      Potential Benefits and risks: The potential benefits of this study include, identifying
      strong risk factors of statin induced muscle symptoms myalgia/myopathy that should inform
      clinical practice in minimizing/ managing severity of statin associated muscle symptoms, by
      identifying patient populations with an increased risk to statin induced myalgia and/or
      myopathy. This information might ultimately inform treatment decisions including drug
      selection and dosing and improved prediction of treatment response in a heterogeneous
      population. The only possible risk in the study is that associated with blood-taking.
      Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle
      stick. Fainting sometimes occurs and infection rarely occurs.
observational model: Cohort
time perspective: Other
measure: Statin drug and metabolite measurement
time frame: 3 to 6 hours
description: Multiple reaction monitoring via a triple quadropole mass spectrometry (MS) platform
measure: Pharmacogenomics associated with statin
time frame: 3 to 6 hours
description: DNA extraction will be performed at GIS using Qiagen QIAamp DNA Blood Maxi kit and will be quantified by pico-green serial dilution assays
For patients who are sensitive about having genetic material collected, investigators will
      provide the option of not having their DNA analyzed in the informed consent form.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 99 Years
healthy volunteers: No
last name: Dr Wei Chieh Jack Tan
role: Principal Investigator
affiliation: National Heart Centre Singapore
last name: Dr Wei Chieh Jack Tan
phone: 67048892
last name: Katherina Oh
phone: 67042290
facility: 
status: Recruiting
contact: 
contact backup: 
country: Singapore
responsible party type: Sponsor
mesh term: Muscular Diseases
mesh term: Drug-Related Side Effects and Adverse Reactions
sharing ipd: No