<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/NCT02252328</url>
  </required_header>
  <id_info>
    <org_study_id>14/0172</org_study_id>
    <secondary_id>2014-003119-13</secondary_id>
    <secondary_id>14/0172</secondary_id>
    <nct_id>NCT02252328</nct_id>
  </id_info>
  <brief_title>Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients</brief_title>
  <official_title>Can Simvastatin Significantly Reduce the Amount of Immunosuppressive Medication Required by Patients With Sight Threatening Uveitis? A Phase 2b, Single Site, Randomized, Placebo Controlled, Double Blinded Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial will compare the effect on disease control and immunosuppression treatment of&#xD;
      adding simvastatin 80mg once daily, over a follow-up and treatment period of 2 years.&#xD;
      Patients will be randomised in a 1:1 fashion to standard treatment with placebo or standard&#xD;
      treatment with the addition of simvastatin (80mg daily). They will be followed at 3 months&#xD;
      intervals for 2 years with a primary end point of mean reduction in corticosteroid dosage at&#xD;
      the 12 month follow-up visit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a non-commercial trial to explore the effect of simvastatin 80mg od on the dose of&#xD;
      corticosteroids and immunosuppression in patients with sight-threatening uveitis.&#xD;
&#xD;
      In order to detect a clinical effect the study is designed as a double blinded, parallel&#xD;
      group, placebo-controlled, randomised trial. Double blinding will be achieved through the use&#xD;
      of a placebo as well as a masked clinical assessor.&#xD;
&#xD;
      Based on the reported effect of simvastatin on brain atrophy among multi[le sclerosis&#xD;
      patients after 12 months treatment, patients will receive treatment or placebo and will be&#xD;
      treated and followed up for 24 months.&#xD;
&#xD;
      Patients randomised to simvastatin will receive a dose of 80mg od. There will be no dose&#xD;
      escalation.&#xD;
&#xD;
      Patients will be reviewed every 3 months and will undergo a complete ophthalmic examination&#xD;
      with treatment adjustment accordingly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2015</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1. Change in dose (mg) of prednisolone after 12 months of treatment</measure>
    <time_frame>12 months</time_frame>
    <description>To determine whether the mean reduction in prednisolone dosage achieved at 12 months is greater in the simvastatin group compared to the placebo treated group?</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The mean reduction in prednisolone achieved at 24 months.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The chnage in the number of 2nd-line immunosuppressive drugs at 24 months</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of disease relapses by 24 months</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood cholesterol and lipid levels at 24 months as compared to baseline</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visual acuity at 12 and 24 months as compared to baseline</measure>
    <time_frame>12 and 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treg and Th17 levels at 12 and 24 months as compared to baseline</measure>
    <time_frame>12 and 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Uveitis</condition>
  <arm_group>
    <arm_group_label>Simvastatine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients receiving simvastatin 80mg once daily in addition to standard care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group of patients receiving placebo once daily in addition to standard care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>Simvastatin 80mg once daily</description>
    <arm_group_label>Simvastatine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must be &gt;18 years and under 80 years.&#xD;
&#xD;
          2. Both sexes may participate, but, because of possible teratogenicity of simvastatin&#xD;
             women may do so only following counselling about the need for adequate contraception.&#xD;
&#xD;
          3. Women of child bearing potential will have to have a negative pregnancy test prior to&#xD;
             enrolment.&#xD;
&#xD;
          4. Patients must have been previously diagnosed with intermediate, posterior or&#xD;
             panuveitis (as defined by the standardization of uveitis nomenclature group).14&#xD;
&#xD;
          5. Patients must be taking systemic prednisolone 10mg once daily or more.&#xD;
&#xD;
          6. Patients may be treated with or without a second line agent.&#xD;
&#xD;
          7. Patients must be willing and able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. No associated underlying systemic disease causing the uveitis.&#xD;
&#xD;
          2. Females of childbearing potential and males must be willing to use an effective method&#xD;
             of contraception (hormonal or barrier method of birth control; abstinence) from the&#xD;
             time consent is signed until 6 weeks after treatment discontinuation.&#xD;
&#xD;
          3. Females of childbearing potential must have a negative pregnancy test within 7 days&#xD;
             prior to being registered for trial treatment.&#xD;
&#xD;
          4. Females must not be breastfeeding.&#xD;
&#xD;
          5. Patients concomitantly taking ciclosporin, fibrates, amiodarone, amlodipine,&#xD;
             verapamil, cytochrome P450 3A4 inhibitors (e.g. itraconazole, ketoconazole,&#xD;
             posaconazole, voriconazole), HIV protease inhibitors (e.g. nelfinavir), erythromycin,&#xD;
             clarithromycin, telithromycin, nefazodone, gemfibrozil, danazol, fusidic acid,&#xD;
             diltiazem or anti-coagulants.&#xD;
&#xD;
          6. Patients will be advised not to drink grapefruit juice during the study.&#xD;
&#xD;
          7. Family history of hereditary muscle disorders.&#xD;
&#xD;
          8. Active Liver disease&#xD;
&#xD;
          9. Severe renal insufficiency.&#xD;
&#xD;
         10. Persistently elevated serum transaminases.&#xD;
&#xD;
         11. Allergies to excipients of simvastatin and placebo&#xD;
&#xD;
         12. Lactose intolerance&#xD;
&#xD;
         13. Involvement in other clinical trials&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oren Tomkins-Netzer, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College, London</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sue Lightman, PhD,FRCOphth</last_name>
    <role>Study Chair</role>
    <affiliation>University College, London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moorfields Eye Hospital</name>
      <address>
        <city>London</city>
        <zip>EC1V 2PD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CR, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.</citation>
    <PMID>24655729</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>October 25, 2017</last_update_submitted>
  <last_update_submitted_qc>October 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Uveitis</keyword>
  <keyword>Simvastatin</keyword>
  <keyword>Visual acuity</keyword>
  <keyword>Corticosteroids</keyword>
  <keyword>Immunosuppression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uveitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simvastatin</mesh_term>
  </intervention_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/NCT02252328
org study id: 14/0172
secondary id: 2014-003119-13
secondary id: 14/0172
nct id: NCT02252328
lead sponsor: 
has dmc: Yes
The trial will compare the effect on disease control and immunosuppression treatment of
      adding simvastatin 80mg once daily, over a follow-up and treatment period of 2 years.
      Patients will be randomised in a 1:1 fashion to standard treatment with placebo or standard
      treatment with the addition of simvastatin (80mg daily). They will be followed at 3 months
      intervals for 2 years with a primary end point of mean reduction in corticosteroid dosage at
      the 12 month follow-up visit.
This is a non-commercial trial to explore the effect of simvastatin 80mg od on the dose of
      corticosteroids and immunosuppression in patients with sight-threatening uveitis.

      In order to detect a clinical effect the study is designed as a double blinded, parallel
      group, placebo-controlled, randomised trial. Double blinding will be achieved through the use
      of a placebo as well as a masked clinical assessor.

      Based on the reported effect of simvastatin on brain atrophy among multi[le sclerosis
      patients after 12 months treatment, patients will receive treatment or placebo and will be
      treated and followed up for 24 months.

      Patients randomised to simvastatin will receive a dose of 80mg od. There will be no dose
      escalation.

      Patients will be reviewed every 3 months and will undergo a complete ophthalmic examination
      with treatment adjustment accordingly.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 1. Change in dose (mg) of prednisolone after 12 months of treatment
time frame: 12 months
description: To determine whether the mean reduction in prednisolone dosage achieved at 12 months is greater in the simvastatin group compared to the placebo treated group?
measure: The mean reduction in prednisolone achieved at 24 months.
time frame: 24 months
measure: The chnage in the number of 2nd-line immunosuppressive drugs at 24 months
time frame: 24 months
measure: The number of disease relapses by 24 months
time frame: 24 months
measure: Blood cholesterol and lipid levels at 24 months as compared to baseline
time frame: 24 months
measure: Change in visual acuity at 12 and 24 months as compared to baseline
time frame: 12 and 24 months
measure: Treg and Th17 levels at 12 and 24 months as compared to baseline
time frame: 12 and 24 months
measure: Number of patients with adverse events.
time frame: 24 months
measure: The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months
time frame: 24 months
arm group label: Simvastatine
arm group type: Experimental
description: Group of patients receiving simvastatin 80mg once daily in addition to standard care
arm group label: Placebo
arm group type: Placebo Comparator
description: Group of patients receiving placebo once daily in addition to standard care
intervention type: Drug
intervention name: Simvastatin
description: Simvastatin 80mg once daily
arm group label: Simvastatine
intervention type: Drug
intervention name: Placebo
description: Placebo tablets once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Oren Tomkins-Netzer, MD, PhD
role: Principal Investigator
affiliation: University College, London
last name: Sue Lightman, PhD,FRCOphth
role: Study Chair
affiliation: University College, London
facility: 
country: United Kingdom
citation: Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CR, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.
PMID: 24655729
responsible party type: Sponsor
mesh term: Uveitis
mesh term: Simvastatin
sharing ipd: No