<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/NCT04412096</url>
  </required_header>
  <id_info>
    <org_study_id>2020H0284</org_study_id>
    <secondary_id>R01EY022124</secondary_id>
    <nct_id>NCT04412096</nct_id>
  </id_info>
  <brief_title>Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance</brief_title>
  <official_title>Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Eye Institute (NEI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to&#xD;
      medications is a critical barrier for the clinician to consistently provide highly effective&#xD;
      IOP-based treatments. Current trial-and-error approaches to glaucoma management are&#xD;
      inefficient and have not addressed this barrier as there are no predictive factors for drug&#xD;
      response. Our long-term goal is to improve outcomes by identifying biomarkers and&#xD;
      environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of&#xD;
      disease progression, &quot;poor response&quot; to treatment, and large IOP fluctuation. Our purpose of&#xD;
      this research project is to address this critical barrier by focusing on physiological&#xD;
      factors that predict IOP response to drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This proposal responded to PA-18-351 &quot;Human Subjects Mechanistic and Minimal Risk Studies&quot;&#xD;
      and qualifies as a clinical trial. The central hypothesis is that variations in IOP response&#xD;
      to glaucoma drugs and IOP fluctuation can be predicted by the aqueous humor dynamic (AHD)&#xD;
      factors that regulate IOP. This hypothesis will be tested in up to 200 participants with&#xD;
      ocular hypertension (OHT) or open-angle glaucoma (OAG). This hypothesis will be tested in two&#xD;
      aims: Aim 1, Test the hypothesis that AHD factors predict the IOP drug response; Aim 2, Test&#xD;
      the hypothesis that aqueous flow and outflow facility predict IOP fluctuation.&#xD;
&#xD;
      The objective is to determine which AHD factors predict a participant's IOP drug response and&#xD;
      IOP fluctuation. The scientific rationale is that AHD parameters (aqueous flow, outflow&#xD;
      facility, episcleral venous pressure, and uveoscleral flow) determine drug response and IOP&#xD;
      fluctuation.&#xD;
&#xD;
      The primary endpoint is IOP response to glaucoma drugs. Exploratory outcome measures include&#xD;
      IOP fluctuation and the AHD measures.&#xD;
&#xD;
      The study population includes participants who have either OHT or OAG. The inclusion and&#xD;
      exclusion criteria described in 5.3, Study Population. The goal is to recruit 150-200&#xD;
      participants over 4 years.&#xD;
&#xD;
      All drugs and instruments used in this study have been FDA approved.&#xD;
&#xD;
      Three sites will enroll participants: Mayo Clinic, The Ohio State University, and University&#xD;
      of Nebraska Medical Center. All sites have experience and expertise with AHD studies in&#xD;
      humans. These study team members have productive collaborations during AHD studies in&#xD;
      controls during the prior NIH funding period. There are no sites outside of the United&#xD;
      States.&#xD;
&#xD;
      The experimental design is a prospective, open-label, clinical trial with randomized cross&#xD;
      over treatment using the topical glaucoma medications, timolol 0.5% and latanoprost 0.005%.&#xD;
      Timolol 0.5% is a beta-blocker and will be dosed as one drop two times a day. Latanoprost&#xD;
      0.005% is a prostaglandin analogue and will be dosed as one drop daily in the evening. The&#xD;
      treatment order will depend on randomization.&#xD;
&#xD;
      AHD measurements are performed at baseline without glaucoma medications. The AHD measurements&#xD;
      include IOP, aqueous humor flow, outflow facility, and episcleral venous pressure.&#xD;
      Uveoscleral outflow is calculated. Some participants who are already taking glaucoma&#xD;
      medications will be washed out in order to assess baseline AHD measurements. An IOP safety&#xD;
      check will be scheduled for those who are washed out of their glaucoma Rx. After baseline AHD&#xD;
      measurements, the AHD measurements are repeated after each of the 7-day drug interventions to&#xD;
      determine the effect of the drug treatment on AHD variables.&#xD;
&#xD;
      There are six study visits, Visits 1 - 6, that include clinical testing, surveys, and AHD&#xD;
      procedures (see 1.2 Schema). Participants will be trained to use the Icare® HOME tonometer to&#xD;
      measure IOP outside of clinic to assess IOP fluctuation.&#xD;
&#xD;
      The study design is a prospective, open-label, randomized order of 7-days treatments with&#xD;
      timolol 0.5% (1 drop two times daily) followed by a washout period and then with latanoprost&#xD;
      0.005% (1 drop daily in the evening) or vice versa. These are referred to as Tx 1 and Tx 2.&#xD;
      IOP safety checks during washout are included for those already taking glaucoma Rx upon&#xD;
      entering the study. IOP response will be determined to each of these medications. AHD factors&#xD;
      will be determined for both study treatments using tonometry, fluorophotometry, tonography,&#xD;
      and episcleral venomanometry. IOP fluctuation will be assessed using the FDA-approved Icare®&#xD;
      HOME tonometer. All test procedures and drugs are FDA approved. There are no experimental&#xD;
      tests or agents.&#xD;
&#xD;
      Sample sizes and power calculations provide rigor to test the hypothesis.&#xD;
&#xD;
      A REDCap database is populated from data on case report forms (CRF), surveys, and the Icare®&#xD;
      HOME tonometer. Data will be analyzed using descriptive statistics of central tendencies and&#xD;
      dispersion, and regression methods in order to understand the individual data in the&#xD;
      distribution of the cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 23, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</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>
    <intervention_model_description>The overall study design is a prospective, open-label, randomized clinical trial with randomized order of 7-day treatments with timolol followed by a washout period and then with latanoprost or vice versa. Participants will undergo two 7-day treatments, with timolol 0.5% (1 drop two times daily) and latanoprost 0.005% (1 drop daily in the evening). The order of timolol and latanoprost will be randomized. The IOP, AHD parameters and IOP fluctuation will be compared in an individual under three conditions: (i) baseline, and after a randomized order of 7-day treatment of (ii) timolol 0.5% 1 drop two times daily and (iii) latanoprost 0.005% 1 drop in the evening separated by a 6-week washout period. The overall time commitment to complete these procedures is three to four months.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation in eye pressures between individuals</measure>
    <time_frame>measurement after 1 week of treatment</time_frame>
    <description>Eye pressure is a steady state quantitative trait that is measured in mm Hg. Eye pressure is determined by the following physiological factors (units of measure): eye fluid or aqueous humor production (microliters/minute), aqueous humor outflow (microliters/minute), outflow resistance (microliters/minute/mm Hg) and venous pressure (mm Hg) of the eye. All of these physiological factors will be determined under baseline condition and under glaucoma drug treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variation in aqueous flow between individuals</measure>
    <time_frame>measurement 1 week after treatment</time_frame>
    <description>Aqueous flow production (microliters/minute) will be determined under baseline condition and under glaucoma drug treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation in episcleral venous pressure</measure>
    <time_frame>measurement 1 week after treatment</time_frame>
    <description>Episcleral venous pressure (mm Hg) of the eye will be determined under baseline condition and under glaucoma drug treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Glaucoma</condition>
  <condition>OHT - Ocular Hypertension</condition>
  <arm_group>
    <arm_group_label>Timolol 0.5%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To compare the variation in response to timolol between individuals</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Latanoprost 0.005%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To compare the variation in response to latanoprost between individuals</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Timolol 0.5% ophthalmic solution</intervention_name>
    <description>1 drop BID</description>
    <arm_group_label>Timolol 0.5%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Latanoprost 0.005% Ophthalmic Solution</intervention_name>
    <description>1 drop QD</description>
    <arm_group_label>Latanoprost 0.005%</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any self-declared ethnicity-race&#xD;
&#xD;
          -  Open-angle with one of the following:&#xD;
&#xD;
               1. Untreated OHT ≥ 21mmHg&#xD;
&#xD;
               2. Treated OHT with history of IOP ≥ 21 mmHg on 2 prior clinic visits or IOP ≥ 21&#xD;
                  mmHg at screening&#xD;
&#xD;
               3. Mild-to-moderate stage open-angle glaucoma based on history of untreated IOP ≥ 21&#xD;
                  mmHg&#xD;
&#xD;
          -  Reliable Humphrey visual field test result within previous 1 year&#xD;
&#xD;
          -  Open on gonioscopy within previous 1 year&#xD;
&#xD;
          -  At least one eye must be phakic&#xD;
&#xD;
          -  Able to cooperate for aqueous humor dynamic procedures&#xD;
&#xD;
          -  Able to participate on site over the multi-visit study period&#xD;
&#xD;
          -  Contact lenses must be removed before topical fluorescein instillation and remain out&#xD;
             until study testing the following day is completed.&#xD;
&#xD;
          -  Contact lenses must be removed for the entire duration of the study visits.&#xD;
&#xD;
          -  All study medication must be used without contact lenses in the eyes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant29 or breastfeeding&#xD;
&#xD;
          -  IOP ≥ 38 in study eye(s) or at discretion of the clinician&#xD;
&#xD;
          -  On more than 2 glaucoma medications&#xD;
&#xD;
          -  Refusal to remove contact lenses&#xD;
&#xD;
          -  Advanced visual field loss (MD ≤ -16 dB) or threat to fixation in study eye(s) or at&#xD;
             discretion of the clinician&#xD;
&#xD;
          -  Study eye(s) with CCT &lt; 480 microns or &gt; than 620 microns&#xD;
&#xD;
          -  Study eye(s) with any sign of Fuchs cornea dystrophy as noted clinically with guttae&#xD;
             and corneal edema&#xD;
&#xD;
          -  Narrow angle of ≤ Shaffer grade 2 for 180o, peripheral synechiae, or peripheral&#xD;
             iridotomy in either eye&#xD;
&#xD;
          -  History of acute angle closure crisis in either eye&#xD;
&#xD;
          -  History of glaucoma incisional surgery (e.g., trabeculectomy, glaucoma drainage&#xD;
             implant, Xen gel stent) in study eye(s)&#xD;
&#xD;
          -  History of minimally invasive glaucoma surgery (MIGS, e.g., angle surgery, Cypass) in&#xD;
             study eye(s)&#xD;
&#xD;
          -  History of any cycloablation surgery (e.g., micropulse or diode transcleral or&#xD;
             endoscopic cyclophotocoagulation) in study eye(s)&#xD;
&#xD;
          -  Study eye cannot have history of any past SLT or ALT glaucoma laser treatments.&#xD;
&#xD;
          -  Study eye(s) cannot have any history of refractive surgery&#xD;
&#xD;
          -  Study eye(s) cannot have any history of herpetic infection of the cornea&#xD;
&#xD;
          -  Study eye(s) cannot have chronic or recurrent inflammatory eye disease&#xD;
&#xD;
          -  Study eye(s) cannot have ocular trauma within the past 6 months, other than&#xD;
             uncomplicated cornea abrasion&#xD;
&#xD;
          -  Study eye(s) cannot have ocular infection in the past 3 months&#xD;
&#xD;
          -  Study eye(s) cannot have clinically significant retinal disease that includes&#xD;
             proliferative diabetic retinopathy, vein occlusion, cystoid macular edema, wet&#xD;
             age-related macular degeneration&#xD;
&#xD;
          -  History of intraocular or peri-ocular injections in study eye(s) within 3 months&#xD;
&#xD;
          -  History of oral steroid use within 30 days of screening Visit 1&#xD;
&#xD;
          -  Any abnormality preventing reliable fluorophotometry (e.g., corneal scarring or severe&#xD;
             dry eye with fluorescein staining)&#xD;
&#xD;
          -  Serious hypersensitivity to any components of study medications or risk from treatment&#xD;
             (e.g., sulfa drug allergy, bradycardia, severe asthma, or emphysema)&#xD;
&#xD;
          -  Participants must be on minimum 30-day stable regimen prior to Visit 1 for a systemic&#xD;
             medication that may affect IOP (i.e., sympathomimetics, beta-blockers,&#xD;
             alpha-adrenergic agonists and blockers, calcium channel blockers, angiotensin&#xD;
             converting enzyme inhibitors, etc.). Any change of such medication during the study&#xD;
             will result in exclusion.&#xD;
&#xD;
          -  Prohibited meds during study: cannabis products, brimonidine 0.025% (Lumify),&#xD;
             bimatoprost 0.03% for eyelash growth (Latisse), topical ocular and peri-ocular&#xD;
             steroids, oral steroids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sayoko Moroi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor and Chair</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Abigail Larsen</last_name>
    <phone>614-293-5287</phone>
    <email>abigail.larsen@osumc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jesse Gilbert</last_name>
    <phone>614-293-5287</phone>
    <email>jesse.gilbert@osumc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arthur Sit, MD</last_name>
      <phone>507-284-2511</phone>
      <email>sit.arthur@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Elainey Wada</last_name>
      <phone>507-538-6543</phone>
      <email>wada.elainey@mayo.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vikas Gulati</last_name>
      <phone>402-559-1853</phone>
      <email>vgulati@unmc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kristi Miller</last_name>
      <phone>402-559-1853</phone>
      <email>kristi.miller@unmc.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sayoko Moroi, MD, PhD</last_name>
      <phone>614-293-5287</phone>
      <email>sayoko.moroi@osumc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Abigail Larsen</last_name>
      <phone>614-293-5287</phone>
      <email>abigail.larsen@osumc.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Man X, Costa R, Ayres BM, Moroi SE. Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris Configuration. Am J Ophthalmol Case Rep. 2016 Oct;3:14-17. doi: 10.1016/j.ajoc.2016.05.003. Epub 2016 May 17.</citation>
    <PMID>29226268</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University</investigator_affiliation>
    <investigator_full_name>Sayoko Moroi</investigator_full_name>
    <investigator_title>Professor and Chair</investigator_title>
  </responsible_party>
  <keyword>aqueous humor dynamics</keyword>
  <keyword>glaucoma</keyword>
  <keyword>eye diseases</keyword>
  <keyword>timolol</keyword>
  <keyword>latanoprost</keyword>
  <keyword>Adrenergic beta-Antagonists</keyword>
  <keyword>Adrenergic Antagonists</keyword>
  <keyword>Adrenergic Agents</keyword>
  <keyword>neurotransmitter agents</keyword>
  <keyword>molecular mechanisms of pharmacological action</keyword>
  <keyword>physiological effects of drugs</keyword>
  <keyword>anti-arrhythmia agents</keyword>
  <keyword>anti-hypertensive agents</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Ocular Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Timolol</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Latanoprost</mesh_term>
    <mesh_term>Ophthalmic Solutions</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/NCT04412096
org study id: 2020H0284
secondary id: R01EY022124
nct id: NCT04412096
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to
      medications is a critical barrier for the clinician to consistently provide highly effective
      IOP-based treatments. Current trial-and-error approaches to glaucoma management are
      inefficient and have not addressed this barrier as there are no predictive factors for drug
      response. Our long-term goal is to improve outcomes by identifying biomarkers and
      environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of
      disease progression, "poor response" to treatment, and large IOP fluctuation. Our purpose of
      this research project is to address this critical barrier by focusing on physiological
      factors that predict IOP response to drugs.
This proposal responded to PA-18-351 "Human Subjects Mechanistic and Minimal Risk Studies"
      and qualifies as a clinical trial. The central hypothesis is that variations in IOP response
      to glaucoma drugs and IOP fluctuation can be predicted by the aqueous humor dynamic (AHD)
      factors that regulate IOP. This hypothesis will be tested in up to 200 participants with
      ocular hypertension (OHT) or open-angle glaucoma (OAG). This hypothesis will be tested in two
      aims: Aim 1, Test the hypothesis that AHD factors predict the IOP drug response; Aim 2, Test
      the hypothesis that aqueous flow and outflow facility predict IOP fluctuation.

      The objective is to determine which AHD factors predict a participant's IOP drug response and
      IOP fluctuation. The scientific rationale is that AHD parameters (aqueous flow, outflow
      facility, episcleral venous pressure, and uveoscleral flow) determine drug response and IOP
      fluctuation.

      The primary endpoint is IOP response to glaucoma drugs. Exploratory outcome measures include
      IOP fluctuation and the AHD measures.

      The study population includes participants who have either OHT or OAG. The inclusion and
      exclusion criteria described in 5.3, Study Population. The goal is to recruit 150-200
      participants over 4 years.

      All drugs and instruments used in this study have been FDA approved.

      Three sites will enroll participants: Mayo Clinic, The Ohio State University, and University
      of Nebraska Medical Center. All sites have experience and expertise with AHD studies in
      humans. These study team members have productive collaborations during AHD studies in
      controls during the prior NIH funding period. There are no sites outside of the United
      States.

      The experimental design is a prospective, open-label, clinical trial with randomized cross
      over treatment using the topical glaucoma medications, timolol 0.5% and latanoprost 0.005%.
      Timolol 0.5% is a beta-blocker and will be dosed as one drop two times a day. Latanoprost
      0.005% is a prostaglandin analogue and will be dosed as one drop daily in the evening. The
      treatment order will depend on randomization.

      AHD measurements are performed at baseline without glaucoma medications. The AHD measurements
      include IOP, aqueous humor flow, outflow facility, and episcleral venous pressure.
      Uveoscleral outflow is calculated. Some participants who are already taking glaucoma
      medications will be washed out in order to assess baseline AHD measurements. An IOP safety
      check will be scheduled for those who are washed out of their glaucoma Rx. After baseline AHD
      measurements, the AHD measurements are repeated after each of the 7-day drug interventions to
      determine the effect of the drug treatment on AHD variables.

      There are six study visits, Visits 1 - 6, that include clinical testing, surveys, and AHD
      procedures (see 1.2 Schema). Participants will be trained to use the Icare® HOME tonometer to
      measure IOP outside of clinic to assess IOP fluctuation.

      The study design is a prospective, open-label, randomized order of 7-days treatments with
      timolol 0.5% (1 drop two times daily) followed by a washout period and then with latanoprost
      0.005% (1 drop daily in the evening) or vice versa. These are referred to as Tx 1 and Tx 2.
      IOP safety checks during washout are included for those already taking glaucoma Rx upon
      entering the study. IOP response will be determined to each of these medications. AHD factors
      will be determined for both study treatments using tonometry, fluorophotometry, tonography,
      and episcleral venomanometry. IOP fluctuation will be assessed using the FDA-approved Icare®
      HOME tonometer. All test procedures and drugs are FDA approved. There are no experimental
      tests or agents.

      Sample sizes and power calculations provide rigor to test the hypothesis.

      A REDCap database is populated from data on case report forms (CRF), surveys, and the Icare®
      HOME tonometer. Data will be analyzed using descriptive statistics of central tendencies and
      dispersion, and regression methods in order to understand the individual data in the
      distribution of the cohort.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The overall study design is a prospective, open-label, randomized clinical trial with randomized order of 7-day treatments with timolol followed by a washout period and then with latanoprost or vice versa. Participants will undergo two 7-day treatments, with timolol 0.5% (1 drop two times daily) and latanoprost 0.005% (1 drop daily in the evening). The order of timolol and latanoprost will be randomized. The IOP, AHD parameters and IOP fluctuation will be compared in an individual under three conditions: (i) baseline, and after a randomized order of 7-day treatment of (ii) timolol 0.5% 1 drop two times daily and (iii) latanoprost 0.005% 1 drop in the evening separated by a 6-week washout period. The overall time commitment to complete these procedures is three to four months.
primary purpose: Treatment
masking: None (Open Label)
measure: Variation in eye pressures between individuals
time frame: measurement after 1 week of treatment
description: Eye pressure is a steady state quantitative trait that is measured in mm Hg. Eye pressure is determined by the following physiological factors (units of measure): eye fluid or aqueous humor production (microliters/minute), aqueous humor outflow (microliters/minute), outflow resistance (microliters/minute/mm Hg) and venous pressure (mm Hg) of the eye. All of these physiological factors will be determined under baseline condition and under glaucoma drug treatment.
measure: Variation in aqueous flow between individuals
time frame: measurement 1 week after treatment
description: Aqueous flow production (microliters/minute) will be determined under baseline condition and under glaucoma drug treatment.
measure: Variation in episcleral venous pressure
time frame: measurement 1 week after treatment
description: Episcleral venous pressure (mm Hg) of the eye will be determined under baseline condition and under glaucoma drug treatment.
arm group label: Timolol 0.5%
arm group type: Experimental
description: To compare the variation in response to timolol between individuals
arm group label: Latanoprost 0.005%
arm group type: Experimental
description: To compare the variation in response to latanoprost between individuals
intervention type: Drug
intervention name: Timolol 0.5% ophthalmic solution
description: 1 drop BID
arm group label: Timolol 0.5%
intervention type: Drug
intervention name: Latanoprost 0.005% Ophthalmic Solution
description: 1 drop QD
arm group label: Latanoprost 0.005%
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Sayoko Moroi, MD, PhD
role: Principal Investigator
affiliation: Professor and Chair
last name: Abigail Larsen
phone: 614-293-5287
email: abigail.larsen@osumc.edu
last name: Jesse Gilbert
phone: 614-293-5287
email: jesse.gilbert@osumc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Man X, Costa R, Ayres BM, Moroi SE. Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris Configuration. Am J Ophthalmol Case Rep. 2016 Oct;3:14-17. doi: 10.1016/j.ajoc.2016.05.003. Epub 2016 May 17.
PMID: 29226268
responsible party type: Principal Investigator
investigator affiliation: Ohio State University
investigator full name: Sayoko Moroi
investigator title: Professor and Chair
mesh term: Glaucoma
mesh term: Ocular Hypertension
mesh term: Timolol
mesh term: Pharmaceutical Solutions
mesh term: Latanoprost
mesh term: Ophthalmic Solutions
sharing ipd: No