<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/NCT02984293</url>
  </required_header>
  <id_info>
    <org_study_id>2016CV05</org_study_id>
    <secondary_id>16/ES/0128</secondary_id>
    <nct_id>NCT02984293</nct_id>
  </id_info>
  <brief_title>Statin Immune Study</brief_title>
  <acronym>ImmunoStat</acronym>
  <official_title>Impact of LILRB5 Genotype on Immune Response to Atorvastatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Dundee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NHS Tayside</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Dundee</source>
  <oversight_info>
    <has_dmc>No</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>
      Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe&#xD;
      drugs. However, up to one third of statin users can experience muscle symptoms, which are&#xD;
      most commonly mild without any conventional laboratory signs of muscle damage. However, these&#xD;
      muscle symptoms can often lead to poor compliance to the cholesterol-lowering therapy,&#xD;
      reducing its effectiveness. Recent data has highlighted the potential role of immune system&#xD;
      in development of statin-induced muscle pain. Variation in the LILRB5 gene has been&#xD;
      associated with statin intolerance. We aim to investigate the impact of LILRB5 genetic&#xD;
      variability in tolerability and immune response to atorvastatin in healthy volunteers.&#xD;
&#xD;
      The study is being undertaken at the Tayside Institute for Cardiovascular Research (TICR) in&#xD;
      Ninewells Hospital, Dundee. We will recruit participants who have donated a sample to GoSHARE&#xD;
      study. The participants will be healthy, and recruited according to their genotype of LILRB5&#xD;
      (information available from GoSHARE). The volunteers will then enter a randomised cross-over&#xD;
      study with two treatment periods. During treatment period one, all participants will be&#xD;
      commenced on atorvastatin or placebo (a dummy drug). Before and at the end of the treatment&#xD;
      period, blood and urine samples will be taken and a muscle symptoms questionnaire will be&#xD;
      completed to assess the tolerability and immune response to the study drug exposure. After&#xD;
      four weeks, the study drug is stopped for a washout period of three weeks before cross-over&#xD;
      commences. Thereafter, during treatment period two, the alternate study drug will be started,&#xD;
      and tolerability will be assessed similar to that in period one. The study will last&#xD;
      approximately 11 weeks. The volunteers have a total of 5 visits to the TICR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 17, 2017</start_date>
  <completion_date type="Actual">November 3, 2017</completion_date>
  <primary_completion_date type="Actual">November 3, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods.</measure>
    <time_frame>Measured at baseline (day 0) and day 29 of both treatment periods.</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Drug Intolerance</condition>
  <arm_group>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The participants will receive atorvastatin (80 mg) orally once daily for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The participants will receive matched placebo orally once daily for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>Atorvastatin 80 mg once daily for 28 days.</description>
    <arm_group_label>Atorvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo once daily for 28 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 40-69 years&#xD;
&#xD;
          -  Statin-naïve&#xD;
&#xD;
          -  White European&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
          -  Acceptable laboratory test results&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant disease&#xD;
&#xD;
          -  Regular drug therapy&#xD;
&#xD;
          -  Recent involvement (&lt;30 days) in a CTIMP&#xD;
&#xD;
          -  Inability/unwillingness to comply with the protocol&#xD;
&#xD;
          -  Carry the rare variant of the CKM polymorphism rs11559024&#xD;
&#xD;
          -  Unable to consent&#xD;
&#xD;
          -  Woman of childbearing potential (i.e. premenopausal female capable of becoming&#xD;
             pregnant)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Colin NA Palmer, PhD FSB FRSE</last_name>
    <role>Study Chair</role>
    <affiliation>University of Dundee</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Dundee</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Dube MP, Zetler R, Barhdadi A, Brown AM, Mongrain I, Normand V, Laplante N, Asselin G, Zada YF, Provost S, Bergeron J, Kouz S, Dufour R, Diaz A, de Denus S, Turgeon J, Rheaume E, Phillips MS, Tardif JC. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.</citation>
    <PMID>25214527</PMID>
  </reference>
  <reference>
    <citation>Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, Carr DF, Bloch KM, Fahy J, Hanson A, Yue QY, Wadelius M, Maitland-van Der Zee AH, Voora D, Psaty BM, Palmer CN, Pirmohamed M. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014 Oct;96(4):470-6. doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.</citation>
    <PMID>24897241</PMID>
  </reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>November 29, 2018</last_update_submitted>
  <last_update_submitted_qc>November 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atorvastatin</keyword>
  <keyword>LILRB5</keyword>
  <keyword>Statin intolerance</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>As per GoSHARE tissue bank protocol, the data derived from the existing samples will be returned to the tissue bank for research use.</ipd_description>
  </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/NCT02984293
org study id: 2016CV05
secondary id: 16/ES/0128
nct id: NCT02984293
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe
      drugs. However, up to one third of statin users can experience muscle symptoms, which are
      most commonly mild without any conventional laboratory signs of muscle damage. However, these
      muscle symptoms can often lead to poor compliance to the cholesterol-lowering therapy,
      reducing its effectiveness. Recent data has highlighted the potential role of immune system
      in development of statin-induced muscle pain. Variation in the LILRB5 gene has been
      associated with statin intolerance. We aim to investigate the impact of LILRB5 genetic
      variability in tolerability and immune response to atorvastatin in healthy volunteers.

      The study is being undertaken at the Tayside Institute for Cardiovascular Research (TICR) in
      Ninewells Hospital, Dundee. We will recruit participants who have donated a sample to GoSHARE
      study. The participants will be healthy, and recruited according to their genotype of LILRB5
      (information available from GoSHARE). The volunteers will then enter a randomised cross-over
      study with two treatment periods. During treatment period one, all participants will be
      commenced on atorvastatin or placebo (a dummy drug). Before and at the end of the treatment
      period, blood and urine samples will be taken and a muscle symptoms questionnaire will be
      completed to assess the tolerability and immune response to the study drug exposure. After
      four weeks, the study drug is stopped for a washout period of three weeks before cross-over
      commences. Thereafter, during treatment period two, the alternate study drug will be started,
      and tolerability will be assessed similar to that in period one. The study will last
      approximately 11 weeks. The volunteers have a total of 5 visits to the TICR.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods.
time frame: Measured at baseline (day 0) and day 29 of both treatment periods.
arm group label: Atorvastatin
arm group type: Active Comparator
description: The participants will receive atorvastatin (80 mg) orally once daily for 28 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: The participants will receive matched placebo orally once daily for 28 days.
intervention type: Drug
intervention name: Atorvastatin
description: Atorvastatin 80 mg once daily for 28 days.
arm group label: Atorvastatin
intervention type: Drug
intervention name: Placebo
description: Placebo once daily for 28 days.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 69 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Colin NA Palmer, PhD FSB FRSE
role: Study Chair
affiliation: University of Dundee
facility: 
country: United Kingdom
citation: Dube MP, Zetler R, Barhdadi A, Brown AM, Mongrain I, Normand V, Laplante N, Asselin G, Zada YF, Provost S, Bergeron J, Kouz S, Dufour R, Diaz A, de Denus S, Turgeon J, Rheaume E, Phillips MS, Tardif JC. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.
PMID: 25214527
citation: Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, Carr DF, Bloch KM, Fahy J, Hanson A, Yue QY, Wadelius M, Maitland-van Der Zee AH, Voora D, Psaty BM, Palmer CN, Pirmohamed M. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014 Oct;96(4):470-6. doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.
PMID: 24897241
responsible party type: Sponsor
mesh term: Atorvastatin
sharing ipd: Yes
ipd description: As per GoSHARE tissue bank protocol, the data derived from the existing samples will be returned to the tissue bank for research use.