<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/NCT03774992</url>
  </required_header>
  <id_info>
    <org_study_id>CONTROL2</org_study_id>
    <nct_id>NCT03774992</nct_id>
  </id_info>
  <brief_title>Clinical Study Of Nearsightedness, TReatment With Orthokeratology Lenses 2</brief_title>
  <acronym>CONTROL2</acronym>
  <official_title>Clinical Study Of Nearsightedness, TReatment With Orthokeratology Lenses 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vejle Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ens Eyes</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vejle Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Myopia is a common disease of the eye with increasing prevalence all over the world including&#xD;
      Denmark where the prevalence has increased from 12,8% in 2004 among young adults (mean age&#xD;
      19,3 years) till 17,9% in 2017 among school children (mean age 15,4 years). High myopia is&#xD;
      associated with an increasing risk of sight threatening complications such as retinal&#xD;
      detachment, glaucoma, macular choroidal degeneration, and myopic choroidal&#xD;
      neovascularization. In myopia the eye is elongated compared to an emmetropic eye. If the&#xD;
      elongation of the eye can be controlled the progression of myopia can be controlled. Asian&#xD;
      studies have shown reduction in axial length growth by 36-46% in children using&#xD;
      orthokeratology contact lenses (OKL). OKL are custom fit, form stable lenses. During sleep&#xD;
      the cornea is reshaped creating an emmetropic vision during the day, so no glasses or contact&#xD;
      lenses are needed.&#xD;
&#xD;
      In the CONTROL-study 60 Danish children aged six to 13 years were randomized 1:1 to either&#xD;
      OKL (intervention group) or single vision spectacles (SVS) (control group) and followed for&#xD;
      18 months to compare changes in axial length (AL). In CONTROL2 the intervention group will be&#xD;
      followed for another 18 month and the control group will be crossed over to OKL treatment.&#xD;
&#xD;
      The aims of CONTROL2 is to:&#xD;
&#xD;
        1. Investigate changes in axial length after 3 years of OKL wear (DreamliteR, Procornea,&#xD;
           Nederlands).&#xD;
&#xD;
        2. Investigate changes in progression rate 18 month before and after OKL wear.&#xD;
&#xD;
        3. Investigate correlations between changes in choroidal thickness and changes in AL.&#xD;
&#xD;
        4. Investigate the safety of OKL treatment (Efron score).&#xD;
&#xD;
        5. Investigate changes in quality of life before and after OKL treatment using Pediatric&#xD;
           Refractive Error Profile 2 (PREP2).&#xD;
&#xD;
        6. Investigate correlations between AC/A-ratio, peripheral refraction and higher order&#xD;
           aberrations on myopia progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Myopia is a common disease of the eye with increasing prevalence in the Western World as well&#xD;
      as in South East Asia where 60-90% of the children are affected. A Danish study found that&#xD;
      early debut of myopia is associated with a higher degree of myopia later on in life. Myopia&#xD;
      may be corrected with spectacles, contact lenses or surgically, but despite this&#xD;
      socio-economic burden, high myopia is associated with an increasing risk of sight threatening&#xD;
      complications such as retinal detachment, glaucoma, macular choroidal degeneration and myopic&#xD;
      choroidal neovascularization.&#xD;
&#xD;
      Myopia is a complex disease with a multi-factorial etiology. Twin studies and family studies&#xD;
      have shown a high heritability for development of myopia, and more than 40 genetic loci have&#xD;
      been identified. Outdoor activity seems to reduce the myopia progression. The shape of the&#xD;
      eye may be of importance; axial growth makes the eye ellipsoidal which increase the&#xD;
      peripheral defocus on the retina. Peripheral defocus has been suggested to induce further&#xD;
      axial growth of the eyeball.&#xD;
&#xD;
      Accommodation is a significant covariant of near work and reading. A cross section study has&#xD;
      shown a reduced precision in accommodation (A) on a near object combined with increased&#xD;
      convergence (C) in myopic eyes. This increased AC/A ratio (dynamic) may be a predictor for&#xD;
      myopia progression.&#xD;
&#xD;
      Interventions for reducing myopia progression have been many. The effects of progressive&#xD;
      additional lenses, multifocal lenses and bifocal lenses have been limited. Anticholinergic&#xD;
      eyedrops (Atropin 0.01%) significantly reduce the progression of myopia in Asian children by&#xD;
      approximately 50% over a period of two years with limited side effects. Almost similar&#xD;
      results have been found in Asian children using orthokeratology contact lenses (OKL) for&#xD;
      reducing myopia progression.&#xD;
&#xD;
      OKL are custom fit, form stable lenses used during sleep. The lenses induce a temporary&#xD;
      flattening of the cornea, which modify or eliminate refractive errors, leaving no need for&#xD;
      glasses or contact lenses during daytime. OKL were introduced in the 1960 ́s, but with&#xD;
      limited success due to lens material (PMMA) which was not gas-permeable. Decentration was&#xD;
      also a problem making the effect variable and unpredictable. With new gas permeable lens&#xD;
      materials and computer assisted topographic measurements of the cornea, fitting of the lenses&#xD;
      has been improved significantly, so that nightly wear is now standard treatment.&#xD;
&#xD;
      A clear-cut reduction in axial length growth in Asian children using OKL compared to&#xD;
      single-vision spectacles (SVS) has been proofed in several studies. In these studies, which&#xD;
      are very heterogeneous regarding design, reductions of 36-46% in axial length growth were&#xD;
      found compared to a matched control group. Two European prospective cohort studies have&#xD;
      investigated the effect of OKL compared to SVS in Spanish children. A reduction in axial&#xD;
      growth of 32 % and 38% respectively was found. Side effects of OKL have been evaluated; in a&#xD;
      meta-analysis from 2015, including 8 Asian and one of the European studies. Odds Ratio for&#xD;
      side effects were 8.87 for the OK group compared to the control group, however all side&#xD;
      effects were mild and disappeared after termination of the treatment.&#xD;
&#xD;
      Thus, a reduction in childhood myopia using OKL has been proofed in Asian children; however,&#xD;
      weather similar result can be achieved in a group of children from Northern Europe is unknown&#xD;
      and to address that the CONTROL-study was conducted. The CONTROL-study is an eighteen-months&#xD;
      randomized prospective 1:1 study of the progression of myopia in a group of Danish children&#xD;
      wearing OKL nightly (n=30) compared to a control group wearing SVS (n=30). The study is&#xD;
      ongoing and thus there are not yet published any results. However, the study has formed the&#xD;
      basis for a unique opportunity to&#xD;
&#xD;
        1. Look at the long-term effects of OKL treatment (3 years) in regards to efficacy and&#xD;
           safety, and&#xD;
&#xD;
        2. Evaluate the progression-rate of myopia 18 months prior to treatment compared to 18&#xD;
           months after treatment with OKL.&#xD;
&#xD;
      Primary goals of the CONTROL2:&#xD;
&#xD;
      1. To investigate changes in axial length after 3 years of OKL wear (DreamliteR, Procornea,&#xD;
      Nederlands).&#xD;
&#xD;
      2. To investigate changes in progression rate 18 month before and after OKL wear.&#xD;
&#xD;
        1. To investigate correlations between changes in choroidal thickness and changes in AL.&#xD;
&#xD;
        2. To investigate the safety of OKL treatment (Efron score).&#xD;
&#xD;
        3. To investigate changes in quality of life before and after OKL treatment using Pediatric&#xD;
           Refractive Error Profile 2 (PREP2).&#xD;
&#xD;
        4. To investigate correlations between AC/A-ratio, peripheral refraction and higher order&#xD;
           aberrations on myopia progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 4, 2018</start_date>
  <completion_date type="Actual">December 1, 2021</completion_date>
  <primary_completion_date type="Actual">December 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Axial length</measure>
    <time_frame>18 months</time_frame>
    <description>Change in axial length (mm)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Myopia</condition>
  <arm_group>
    <arm_group_label>Orthokeratology</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to OKL in the CONTROL-study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cross over</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to SVS in the CONTROL-study</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Orthokeratology lenses</intervention_name>
    <description>Custom fit, form stable contact lenses</description>
    <arm_group_label>Cross over</arm_group_label>
    <arm_group_label>Orthokeratology</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  subjects enrolled in the CONTROL-study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  none&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Flemming Møller, Dr. med</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vejle Hospital and University of Southern Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vejle Hospital</name>
      <address>
        <city>Vejle</city>
        <state>Jylland</state>
        <zip>7100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>March 3, 2022</last_update_submitted>
  <last_update_submitted_qc>March 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Orthokeratology lenses</keyword>
  <keyword>Myopia</keyword>
  <keyword>Children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myopia</mesh_term>
  </condition_browse>
  <!-- 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/NCT03774992
org study id: CONTROL2
nct id: NCT03774992
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Myopia is a common disease of the eye with increasing prevalence all over the world including
      Denmark where the prevalence has increased from 12,8% in 2004 among young adults (mean age
      19,3 years) till 17,9% in 2017 among school children (mean age 15,4 years). High myopia is
      associated with an increasing risk of sight threatening complications such as retinal
      detachment, glaucoma, macular choroidal degeneration, and myopic choroidal
      neovascularization. In myopia the eye is elongated compared to an emmetropic eye. If the
      elongation of the eye can be controlled the progression of myopia can be controlled. Asian
      studies have shown reduction in axial length growth by 36-46% in children using
      orthokeratology contact lenses (OKL). OKL are custom fit, form stable lenses. During sleep
      the cornea is reshaped creating an emmetropic vision during the day, so no glasses or contact
      lenses are needed.

      In the CONTROL-study 60 Danish children aged six to 13 years were randomized 1:1 to either
      OKL (intervention group) or single vision spectacles (SVS) (control group) and followed for
      18 months to compare changes in axial length (AL). In CONTROL2 the intervention group will be
      followed for another 18 month and the control group will be crossed over to OKL treatment.

      The aims of CONTROL2 is to:

        1. Investigate changes in axial length after 3 years of OKL wear (DreamliteR, Procornea,
           Nederlands).

        2. Investigate changes in progression rate 18 month before and after OKL wear.

        3. Investigate correlations between changes in choroidal thickness and changes in AL.

        4. Investigate the safety of OKL treatment (Efron score).

        5. Investigate changes in quality of life before and after OKL treatment using Pediatric
           Refractive Error Profile 2 (PREP2).

        6. Investigate correlations between AC/A-ratio, peripheral refraction and higher order
           aberrations on myopia progression.
Myopia is a common disease of the eye with increasing prevalence in the Western World as well
      as in South East Asia where 60-90% of the children are affected. A Danish study found that
      early debut of myopia is associated with a higher degree of myopia later on in life. Myopia
      may be corrected with spectacles, contact lenses or surgically, but despite this
      socio-economic burden, high myopia is associated with an increasing risk of sight threatening
      complications such as retinal detachment, glaucoma, macular choroidal degeneration and myopic
      choroidal neovascularization.

      Myopia is a complex disease with a multi-factorial etiology. Twin studies and family studies
      have shown a high heritability for development of myopia, and more than 40 genetic loci have
      been identified. Outdoor activity seems to reduce the myopia progression. The shape of the
      eye may be of importance; axial growth makes the eye ellipsoidal which increase the
      peripheral defocus on the retina. Peripheral defocus has been suggested to induce further
      axial growth of the eyeball.

      Accommodation is a significant covariant of near work and reading. A cross section study has
      shown a reduced precision in accommodation (A) on a near object combined with increased
      convergence (C) in myopic eyes. This increased AC/A ratio (dynamic) may be a predictor for
      myopia progression.

      Interventions for reducing myopia progression have been many. The effects of progressive
      additional lenses, multifocal lenses and bifocal lenses have been limited. Anticholinergic
      eyedrops (Atropin 0.01%) significantly reduce the progression of myopia in Asian children by
      approximately 50% over a period of two years with limited side effects. Almost similar
      results have been found in Asian children using orthokeratology contact lenses (OKL) for
      reducing myopia progression.

      OKL are custom fit, form stable lenses used during sleep. The lenses induce a temporary
      flattening of the cornea, which modify or eliminate refractive errors, leaving no need for
      glasses or contact lenses during daytime. OKL were introduced in the 1960 ́s, but with
      limited success due to lens material (PMMA) which was not gas-permeable. Decentration was
      also a problem making the effect variable and unpredictable. With new gas permeable lens
      materials and computer assisted topographic measurements of the cornea, fitting of the lenses
      has been improved significantly, so that nightly wear is now standard treatment.

      A clear-cut reduction in axial length growth in Asian children using OKL compared to
      single-vision spectacles (SVS) has been proofed in several studies. In these studies, which
      are very heterogeneous regarding design, reductions of 36-46% in axial length growth were
      found compared to a matched control group. Two European prospective cohort studies have
      investigated the effect of OKL compared to SVS in Spanish children. A reduction in axial
      growth of 32 % and 38% respectively was found. Side effects of OKL have been evaluated; in a
      meta-analysis from 2015, including 8 Asian and one of the European studies. Odds Ratio for
      side effects were 8.87 for the OK group compared to the control group, however all side
      effects were mild and disappeared after termination of the treatment.

      Thus, a reduction in childhood myopia using OKL has been proofed in Asian children; however,
      weather similar result can be achieved in a group of children from Northern Europe is unknown
      and to address that the CONTROL-study was conducted. The CONTROL-study is an eighteen-months
      randomized prospective 1:1 study of the progression of myopia in a group of Danish children
      wearing OKL nightly (n=30) compared to a control group wearing SVS (n=30). The study is
      ongoing and thus there are not yet published any results. However, the study has formed the
      basis for a unique opportunity to

        1. Look at the long-term effects of OKL treatment (3 years) in regards to efficacy and
           safety, and

        2. Evaluate the progression-rate of myopia 18 months prior to treatment compared to 18
           months after treatment with OKL.

      Primary goals of the CONTROL2:

      1. To investigate changes in axial length after 3 years of OKL wear (DreamliteR, Procornea,
      Nederlands).

      2. To investigate changes in progression rate 18 month before and after OKL wear.

        1. To investigate correlations between changes in choroidal thickness and changes in AL.

        2. To investigate the safety of OKL treatment (Efron score).

        3. To investigate changes in quality of life before and after OKL treatment using Pediatric
           Refractive Error Profile 2 (PREP2).

        4. To investigate correlations between AC/A-ratio, peripheral refraction and higher order
           aberrations on myopia progression.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Axial length
time frame: 18 months
description: Change in axial length (mm)
arm group label: Orthokeratology
arm group type: Experimental
description: Subjects randomized to OKL in the CONTROL-study
arm group label: Cross over
arm group type: Experimental
description: Subjects randomized to SVS in the CONTROL-study
intervention type: Device
intervention name: Orthokeratology lenses
description: Custom fit, form stable contact lenses
arm group label: Cross over
arm group label: Orthokeratology
criteria: 
gender: All
minimum age: 7 Years
maximum age: 14 Years
healthy volunteers: No
last name: Flemming Møller, Dr. med
role: Principal Investigator
affiliation: Vejle Hospital and University of Southern Denmark
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Myopia