<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/NCT03250819</url>
  </required_header>
  <id_info>
    <org_study_id>NL58992.068.17</org_study_id>
    <nct_id>NCT03250819</nct_id>
  </id_info>
  <brief_title>Gene Polymorphisms of Corticosteroid-induced Ocular Hypertension</brief_title>
  <official_title>Genetic Association Study on Corticosteroid-induced Elevation of the Intraocular Pressure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</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>
      Glaucoma is one of the most prevalent eye diseases and the second most common cause of&#xD;
      blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is&#xD;
      a slowly progressing neuropathy of the optic nerve that causes loss of visual field and&#xD;
      eventually blindness. Elevated intra-ocular pressure (IOP) is the most important risk factor.&#xD;
&#xD;
      Corticosteroids, which are often used for the treatment of many diseases in ophthalmology and&#xD;
      other specialities, may cause an elevation of the IOP. It is estimated that corticosteroids&#xD;
      induce ocular hypertension in approximately 18%-36% of the general population and in patients&#xD;
      with POAG this percentage can be as high as 92%. When the treatment is sustained, this can&#xD;
      cause a glaucomatous neuropathy of the optic nerve (corticosteroid-induced glaucoma).&#xD;
&#xD;
      The precise pathogenic mechanism isn't clear yet. Genetic factors are likely to affect the&#xD;
      susceptibility to corticosteroid response. Therefore, an overview of the genetic mechanisms&#xD;
      of corticosteroid-induced glaucoma can give more insight in the pathogenesis. In this study&#xD;
      the researchers investigate the occurrence of SNPs (single nucleotide polymorphisms) in 150&#xD;
      cases with a steroid-response in comparison with 300 controls exposed to corticosteroids&#xD;
      without a steroid-response.&#xD;
&#xD;
      Up to now, one small GWAS has been conducted comparing 32 patients with and without&#xD;
      corticosteroid-induced ocular hypertension after treatment with intravitreal triamcinolone.&#xD;
      In this study, two SNPs proximal of the transcriptional start site (near the 5') of HCG22 on&#xD;
      chromosome 6 were identified. However, this is a rather small sample population and the&#xD;
      investigators didn't match for the underlying disease. Further, in another small study,&#xD;
      Hogewind et al. performed SNP analysis in multiple genes (SFRS3, FKBP4, FKBP5, and NR3C1) in&#xD;
      corticosteroid-induced ocular hypertension.&#xD;
&#xD;
      This study enables the investigators to identify patients at risk for developing&#xD;
      corticosteroid-induced glaucoma and to gain a better insight in the pathogenesis. This may&#xD;
      also lead to the discovery of biomarkers that indicate an increased risk of developing a&#xD;
      steroid-induced glaucoma and new prevention and treatment strategies, which are necessary as&#xD;
      the treatment of corticosteroid induced-glaucoma now only focuses at lowering the IOP and can&#xD;
      still be challenging.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">May 1, 2020</completion_date>
  <primary_completion_date type="Actual">February 6, 2019</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>Differences in SNP's in corticosteroid responders and non-responders</measure>
    <time_frame>At the time of inclusion</time_frame>
    <description>What are the differences in SNPs in patients with corticosteroid-induced ocular hypertension in comparison with patients exposed to corticosteroids who do not respond with an IOP increase</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">370</enrollment>
  <condition>Corticosteroid Induced Ocular Hypertension/Glaucoma</condition>
  <arm_group>
    <arm_group_label>Corticosteroid responders</arm_group_label>
    <description>Patients who develop an increase in eye pressure after the use of corticosteroids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-corticosteroid responders</arm_group_label>
    <description>Patients who use/used corticosteroids but didn't develop an increase in eye pressure</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SNP analysis</intervention_name>
    <description>The collected blood samples will be used to investigate the occurrence of SNPs (single nucleotide polymorphisms) in both study groups</description>
    <arm_group_label>Corticosteroid responders</arm_group_label>
    <arm_group_label>Non-corticosteroid responders</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who started topical, intravitreal or subconjunctival corticosteroids will be&#xD;
        included at the University Eye Clinic Maastricht of the Maastricht University Medical&#xD;
        Centre+, the Netherlands. The participants will be divided in two groups: cases who are&#xD;
        corticosteroid responder (n=150) and controls exposed to corticosteroids who did not&#xD;
        respond with an IOP increase (n=300).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Use of corticosteroids:&#xD;
&#xD;
          -  Patients treated with Ozurdex (an intravitreal dexamethasone implant&#xD;
&#xD;
          -  Patients treated with subconjunctival Triamcinolone/ Celestone injections&#xD;
&#xD;
          -  Patients treated with corticosteroids after a corneal surgery&#xD;
&#xD;
          -  Patients treated with corticosteroids after a refractive surgery&#xD;
&#xD;
          -  Patients treated with corticosteroids after a cataract surgery&#xD;
&#xD;
          -  Patients treated with corticosteroids for macular edema&#xD;
&#xD;
          -  Patients exposed to corticosteroids for other diseases such as uveitis&#xD;
&#xD;
          -  When using topical corticosteroids, time of use &gt; 3 months&#xD;
&#xD;
          -  Age &gt; 18 year and mentally competent&#xD;
&#xD;
          -  Patient from the Maastricht University Medical Centre+ (MUMC+), the Netherlands&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 year&#xD;
&#xD;
          -  Mentally not able to participate or give permission&#xD;
&#xD;
          -  Not able to communicate in Dutch&#xD;
&#xD;
          -  Patients with a type of uveitis that might cause a decrease of the IOP&#xD;
&#xD;
          -  When using topical corticosteroids, time of use &lt; 3 months.&#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>Johannes SA Schouten, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Eye Clinic Maastricht, Maastricht UMC+</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Jeong S, Patel N, Edlund CK, Hartiala J, Hazelett DJ, Itakura T, Wu PC, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito CA, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2737-48. doi: 10.1167/iovs.14-14803.</citation>
    <PMID>25813999</PMID>
  </reference>
  <reference>
    <citation>Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.</citation>
    <PMID>27666015</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2020</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>Ocular Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03250819
org study id: NL58992.068.17
nct id: NCT03250819
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Glaucoma is one of the most prevalent eye diseases and the second most common cause of
      blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is
      a slowly progressing neuropathy of the optic nerve that causes loss of visual field and
      eventually blindness. Elevated intra-ocular pressure (IOP) is the most important risk factor.

      Corticosteroids, which are often used for the treatment of many diseases in ophthalmology and
      other specialities, may cause an elevation of the IOP. It is estimated that corticosteroids
      induce ocular hypertension in approximately 18%-36% of the general population and in patients
      with POAG this percentage can be as high as 92%. When the treatment is sustained, this can
      cause a glaucomatous neuropathy of the optic nerve (corticosteroid-induced glaucoma).

      The precise pathogenic mechanism isn't clear yet. Genetic factors are likely to affect the
      susceptibility to corticosteroid response. Therefore, an overview of the genetic mechanisms
      of corticosteroid-induced glaucoma can give more insight in the pathogenesis. In this study
      the researchers investigate the occurrence of SNPs (single nucleotide polymorphisms) in 150
      cases with a steroid-response in comparison with 300 controls exposed to corticosteroids
      without a steroid-response.

      Up to now, one small GWAS has been conducted comparing 32 patients with and without
      corticosteroid-induced ocular hypertension after treatment with intravitreal triamcinolone.
      In this study, two SNPs proximal of the transcriptional start site (near the 5') of HCG22 on
      chromosome 6 were identified. However, this is a rather small sample population and the
      investigators didn't match for the underlying disease. Further, in another small study,
      Hogewind et al. performed SNP analysis in multiple genes (SFRS3, FKBP4, FKBP5, and NR3C1) in
      corticosteroid-induced ocular hypertension.

      This study enables the investigators to identify patients at risk for developing
      corticosteroid-induced glaucoma and to gain a better insight in the pathogenesis. This may
      also lead to the discovery of biomarkers that indicate an increased risk of developing a
      steroid-induced glaucoma and new prevention and treatment strategies, which are necessary as
      the treatment of corticosteroid induced-glaucoma now only focuses at lowering the IOP and can
      still be challenging.
observational model: Cohort
time perspective: Other
measure: Differences in SNP's in corticosteroid responders and non-responders
time frame: At the time of inclusion
description: What are the differences in SNPs in patients with corticosteroid-induced ocular hypertension in comparison with patients exposed to corticosteroids who do not respond with an IOP increase
arm group label: Corticosteroid responders
description: Patients who develop an increase in eye pressure after the use of corticosteroids
arm group label: Non-corticosteroid responders
description: Patients who use/used corticosteroids but didn't develop an increase in eye pressure
intervention type: Other
intervention name: SNP analysis
description: The collected blood samples will be used to investigate the occurrence of SNPs (single nucleotide polymorphisms) in both study groups
arm group label: Corticosteroid responders
arm group label: Non-corticosteroid responders
Whole blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johannes SA Schouten, MD, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
citation: Jeong S, Patel N, Edlund CK, Hartiala J, Hazelett DJ, Itakura T, Wu PC, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito CA, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2737-48. doi: 10.1167/iovs.14-14803.
PMID: 25813999
citation: Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.
PMID: 27666015
responsible party type: Sponsor
mesh term: Ocular Hypertension
mesh term: Hypertension
sharing ipd: Undecided