xml: <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/NCT06035887</url>
    </required_header>
    <id_info>
      <org_study_id>IRAS 317611</org_study_id>
      <nct_id>NCT06035887</nct_id>
    </id_info>
    <brief_title>Novel ERG for Detection of Hydroxychloroquine Retinopathy</brief_title>
    <official_title>A Feasibility Study Using Novel, Portable Electroretinography Devices to Detect Hydroxychloroquine Retinopathy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>King's College Hospital NHS Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>LUPUS UK</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>King's College Hospital Charity</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>King's College Hospital NHS Trust</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of the study is to investigate novel electroretinography (ERG) devices in the&#xD;
        detection of hydroxychloroquine retinopathy. Two devices (the RETEval full-field and flicker&#xD;
        ERG and UTAS multifocal ERG) will be evaluated in this study, comparing device outputs to&#xD;
        standard of care screening tests, in groups of participants characterised by presence or&#xD;
        absence of hydroxychloroquine-related retinopathy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hydroxychloroquine (HCQ) is a widely used drug used to treat disorders of inflammation in the&#xD;
        body with up to 320,000 people estimated to be on this drug in the UK alone. Retinopathy due&#xD;
        to HCQ is a significant problem, necessitating yearly screening which can only realistically&#xD;
        take place in hospital eye units where funding and capacity constraints limit the provision&#xD;
        of services.&#xD;
  &#xD;
        Electroretinography is a non-invasive method of testing for eye retinal problems, which works&#xD;
        by flashing light (in certain patterns and brightness) into eyes and measuring the electrical&#xD;
        response through fine wires placed on the eye surface or behind the eyelid, and is considered&#xD;
        by many authors to be a gold-standard test to detect HCQ retinopathy. Their use has been&#xD;
        limited due to the high expertise required to undertake and interpret tests, limited&#xD;
        availability of testing, and high test burden, however newer electroretinography devices have&#xD;
        been developed by a company called LKC Technologies, which are faster to perform, use leads&#xD;
        placed on the skin (rather than the eye surface) which are more comfortable, easier to use by&#xD;
        healthcare technicians, and can be done without the need for dilating eyedrops. The two&#xD;
        devices being tested in this study are:&#xD;
  &#xD;
          -  The RETEval = a handheld electroretinography testing device&#xD;
  &#xD;
          -  The UTAS multifocal ERG = a trolley-mounted electroretinography testing device&#xD;
  &#xD;
        These innovations may make testing far easier to develop in both hospital eye service, and&#xD;
        potentially even general settings such as outpatient clinics, general practices, and&#xD;
        optometrists. This study aims to evaluate the performance of devices to detect and classify&#xD;
        participants in 4 main groups:&#xD;
  &#xD;
          -  Normative control participants (n=35)&#xD;
  &#xD;
          -  Patients taking HCQ but without retinopathy (n=35)&#xD;
  &#xD;
          -  Patients taking HCQ with indeterminate features of retinopathy (also known as POSSIBLE&#xD;
             retinopathy) (n=35)&#xD;
  &#xD;
          -  Patients taking HCQ with definite retinopathy&#xD;
  &#xD;
        Device outputs will be analysed and compared with masked graded screening results&#xD;
        (incorporating spectral-domain macular optical coherence tomography and autofluorescence as&#xD;
        standard, taken on the same visit) to generate device- and device-output-specific&#xD;
        sensitivities and specificities. If a signal is found, the feasibility outcomes from this&#xD;
        study will inform the study methodology and timelines for a larger trial if necessary.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2023</start_date>
    <completion_date type="Anticipated">November 2025</completion_date>
    <primary_completion_date type="Anticipated">November 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests</measure>
      <time_frame>All tests required to determine sensitivity and specificity of both devices compared to standard retinal imaging will be completed in a single visit. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Primary Outcome</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To compare the sensitivity and specificity of undilated versus dilated testing with the multifocal ERG device, for all categories of hydroxychloroquine retinopathy</measure>
      <time_frame>All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Secondary Outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To determine the patient acceptability of both devices evaluated using standardised, study-specific questionnaires</measure>
      <time_frame>All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Feasibility Outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To determine the proportion and recruitment rate of patients in each category of hydroxychloroquine retinopathy who consent to join this study.</measure>
      <time_frame>All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Feasibility Outcome</description>
    </secondary_outcome>
    <other_outcome>
      <measure>To determine which ERG waveform features (such as implicit time or amplitude) from both devices best discriminate participants with NO hydroxychloroquine retinopathy from those with POSSIBLE and DEFINITE hydroxychloroquine retinopathy</measure>
      <time_frame>All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Exploratory Outcome</description>
    </other_outcome>
    <other_outcome>
      <measure>To determine if both device waveforms correlate with standard mfERG waveforms in patients receiving hydroxychloroquine</measure>
      <time_frame>All tests required to determine this outcome will be completed at a single visit. Novel device ERG waveforms will be compared with standard mfERG where undertaken in the preceding 12 months. Safety will be evaluated up to 1 week post-visit.</time_frame>
      <description>Exploratory Outcome</description>
    </other_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">140</enrollment>
    <condition>Hydroxychloroquine Retinopathy</condition>
    <arm_group>
      <arm_group_label>Normative Controls</arm_group_label>
      <description>Age- and sex- matched normal controls</description>
    </arm_group>
    <arm_group>
      <arm_group_label>On Hydroxychloroquine, NO retinopathy</arm_group_label>
      <description>Participants over 18 years on hydroxychloroquine without hydroxychloroquine-related retinopathy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>On Hydroxychloroquine, POSSIBLE retinopathy</arm_group_label>
      <description>Participants over 18 years on hydroxychloroquine with possible (indeterminate) hydroxychloroquine-related retinopathy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>On Hydroxychloroquine, DEFINITE retinopathy</arm_group_label>
      <description>Participants over 18 years on hydroxychloroquine with definite hydroxychloroquine-related retinopathy</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated)</intervention_name>
      <description>RETEval Complete hand-held electroretinogram</description>
      <arm_group_label>Normative Controls</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, DEFINITE retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, NO retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, POSSIBLE retinopathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated)</intervention_name>
      <description>UTAS multifocal electroretinogram</description>
      <arm_group_label>Normative Controls</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, DEFINITE retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, NO retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, POSSIBLE retinopathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Spectral-Domain Optical Coherence Tomography (Standard of Care test)</intervention_name>
      <description>Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan)</description>
      <arm_group_label>Normative Controls</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, DEFINITE retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, NO retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, POSSIBLE retinopathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Macular Autofluorescence (Standard of Care test)</intervention_name>
      <description>Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)</description>
      <arm_group_label>Normative Controls</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, DEFINITE retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, NO retinopathy</arm_group_label>
      <arm_group_label>On Hydroxychloroquine, POSSIBLE retinopathy</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Age- and sex-matched control group (n=35) On hydroxychloroquine without retinopathy (n=35)&#xD;
          On hydroxychloroquine with possible retinopathy (n=35) On hydroxychloroquine with definite&#xD;
          retinopathy (n=35)&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years&#xD;
  &#xD;
            2. HCQ groups:&#xD;
  &#xD;
               a. HCQ use &gt;5 years for patients without any high-risk factors, or &gt;1 year in patients&#xD;
               with one or more high-risk factors for HCQ retinopathy, namely: i. Dose &gt;5mg/kg per&#xD;
               day actual body weight (ABW) ii. Estimated glomerular filtration rate (eGFR) of&#xD;
               &lt;60mls/min/1.73m2 iii. Concomitant tamoxifen use&#xD;
  &#xD;
            3. Control group:&#xD;
  &#xD;
                 1. No prior HCQ exposure&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Cataract grade ≥3 of any subtype&#xD;
  &#xD;
            2. Recent cataract surgery within 4 weeks of recruitment&#xD;
  &#xD;
            3. Significant media opacity or corneal disease including, but not limited to, corneal&#xD;
               oedema, corneal scarring, keratoconus, previous corneal transplants, severe&#xD;
               keratoconjunctivitis sicca (requiring the use of topical serum, immunosuppressive or&#xD;
               analogous therapy, or procedural treatment).&#xD;
  &#xD;
            4. Significant macular co-pathology including, but not limited to, macular degeneration,&#xD;
               macular scarring, cystic macular oedema (for any reason), staphyloma.&#xD;
  &#xD;
            5. Inherited retinal and/or macular dystrophies including colour vision deficiencies&#xD;
  &#xD;
            6. Active or previous posterior uveitis or pan-uveitis&#xD;
  &#xD;
            7. Aphakia&#xD;
  &#xD;
            8. High refractive error &gt;6.00 dioptres&#xD;
  &#xD;
            9. Amblyopia&#xD;
  &#xD;
           10. Diabetes&#xD;
  &#xD;
           11. Retinal angiopathies including, but no limited to, retinal vein occlusion, retinal&#xD;
               artery occlusion, ocular ischaemic syndrome, HIV retinopathy, Sickle cell disease,&#xD;
               radiation retinopathy&#xD;
  &#xD;
           12. Visually significant surgical retinal disease including epiretinal membrane, macular&#xD;
               hole, retinal detachment, retinal tear&#xD;
  &#xD;
           13. Previous retinal laser or intravitreal treatment&#xD;
  &#xD;
           14. Moderate or worse glaucoma&#xD;
  &#xD;
           15. Optic atrophy&#xD;
  &#xD;
           16. Photosensitive epilepsy&#xD;
  &#xD;
           17. Ungradable HCQ retinopathy screening images&#xD;
  &#xD;
           18. Periocular infection or rash (recruitment can be deferred until acute pathology has&#xD;
               resolved)&#xD;
  &#xD;
           19. Unable or unwilling to undertake study activities&#xD;
  &#xD;
           20. Any active use or history of the following medications:&#xD;
  &#xD;
          Amiodarone Canthaxanthin Deferoxamine Digoxin Ethambutol Interferon-alpha Melatonin&#xD;
          Nefazodone Sildenafil Vigabatrin Chloroquine Quinine&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Professor Timothy L Jackson</last_name>
      <role>Study Chair</role>
      <affiliation>King's College Hospital NHS Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Professor Timothy L Jackson</last_name>
      <phone>020 3299 1297</phone>
      <email>t.jackson1@nhs.net</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Dr Chan Ning Lee</last_name>
      <phone>020 3299 1297</phone>
      <email>channing.lee2@nhs.net</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 29, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Electroretinography</keyword>
    <keyword>Diagnostic Evaluation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Retinal Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06035887
  org study id: IRAS 317611
  nct id: NCT06035887
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  The purpose of the study is to investigate novel electroretinography (ERG) devices in the
        detection of hydroxychloroquine retinopathy. Two devices (the RETEval full-field and flicker
        ERG and UTAS multifocal ERG) will be evaluated in this study, comparing device outputs to
        standard of care screening tests, in groups of participants characterised by presence or
        absence of hydroxychloroquine-related retinopathy.
  Hydroxychloroquine (HCQ) is a widely used drug used to treat disorders of inflammation in the
        body with up to 320,000 people estimated to be on this drug in the UK alone. Retinopathy due
        to HCQ is a significant problem, necessitating yearly screening which can only realistically
        take place in hospital eye units where funding and capacity constraints limit the provision
        of services.
  
        Electroretinography is a non-invasive method of testing for eye retinal problems, which works
        by flashing light (in certain patterns and brightness) into eyes and measuring the electrical
        response through fine wires placed on the eye surface or behind the eyelid, and is considered
        by many authors to be a gold-standard test to detect HCQ retinopathy. Their use has been
        limited due to the high expertise required to undertake and interpret tests, limited
        availability of testing, and high test burden, however newer electroretinography devices have
        been developed by a company called LKC Technologies, which are faster to perform, use leads
        placed on the skin (rather than the eye surface) which are more comfortable, easier to use by
        healthcare technicians, and can be done without the need for dilating eyedrops. The two
        devices being tested in this study are:
  
          -  The RETEval = a handheld electroretinography testing device
  
          -  The UTAS multifocal ERG = a trolley-mounted electroretinography testing device
  
        These innovations may make testing far easier to develop in both hospital eye service, and
        potentially even general settings such as outpatient clinics, general practices, and
        optometrists. This study aims to evaluate the performance of devices to detect and classify
        participants in 4 main groups:
  
          -  Normative control participants (n=35)
  
          -  Patients taking HCQ but without retinopathy (n=35)
  
          -  Patients taking HCQ with indeterminate features of retinopathy (also known as POSSIBLE
             retinopathy) (n=35)
  
          -  Patients taking HCQ with definite retinopathy
  
        Device outputs will be analysed and compared with masked graded screening results
        (incorporating spectral-domain macular optical coherence tomography and autofluorescence as
        standard, taken on the same visit) to generate device- and device-output-specific
        sensitivities and specificities. If a signal is found, the feasibility outcomes from this
        study will inform the study methodology and timelines for a larger trial if necessary.
  observational model: Case-Control
  time perspective: Prospective
  measure: The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests
  time frame: All tests required to determine sensitivity and specificity of both devices compared to standard retinal imaging will be completed in a single visit. Safety will be evaluated up to 1 week post-visit.
  description: Primary Outcome
  measure: To compare the sensitivity and specificity of undilated versus dilated testing with the multifocal ERG device, for all categories of hydroxychloroquine retinopathy
  time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
  description: Secondary Outcome
  measure: To determine the patient acceptability of both devices evaluated using standardised, study-specific questionnaires
  time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
  description: Feasibility Outcome
  measure: To determine the proportion and recruitment rate of patients in each category of hydroxychloroquine retinopathy who consent to join this study.
  time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
  description: Feasibility Outcome
  measure: To determine which ERG waveform features (such as implicit time or amplitude) from both devices best discriminate participants with NO hydroxychloroquine retinopathy from those with POSSIBLE and DEFINITE hydroxychloroquine retinopathy
  time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
  description: Exploratory Outcome
  measure: To determine if both device waveforms correlate with standard mfERG waveforms in patients receiving hydroxychloroquine
  time frame: All tests required to determine this outcome will be completed at a single visit. Novel device ERG waveforms will be compared with standard mfERG where undertaken in the preceding 12 months. Safety will be evaluated up to 1 week post-visit.
  description: Exploratory Outcome
  arm group label: Normative Controls
  description: Age- and sex- matched normal controls
  arm group label: On Hydroxychloroquine, NO retinopathy
  description: Participants over 18 years on hydroxychloroquine without hydroxychloroquine-related retinopathy
  arm group label: On Hydroxychloroquine, POSSIBLE retinopathy
  description: Participants over 18 years on hydroxychloroquine with possible (indeterminate) hydroxychloroquine-related retinopathy
  arm group label: On Hydroxychloroquine, DEFINITE retinopathy
  description: Participants over 18 years on hydroxychloroquine with definite hydroxychloroquine-related retinopathy
  intervention type: Diagnostic Test
  intervention name: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated)
  description: RETEval Complete hand-held electroretinogram
  arm group label: Normative Controls
  arm group label: On Hydroxychloroquine, DEFINITE retinopathy
  arm group label: On Hydroxychloroquine, NO retinopathy
  arm group label: On Hydroxychloroquine, POSSIBLE retinopathy
  intervention type: Diagnostic Test
  intervention name: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated)
  description: UTAS multifocal electroretinogram
  arm group label: Normative Controls
  arm group label: On Hydroxychloroquine, DEFINITE retinopathy
  arm group label: On Hydroxychloroquine, NO retinopathy
  arm group label: On Hydroxychloroquine, POSSIBLE retinopathy
  intervention type: Diagnostic Test
  intervention name: Spectral-Domain Optical Coherence Tomography (Standard of Care test)
  description: Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan)
  arm group label: Normative Controls
  arm group label: On Hydroxychloroquine, DEFINITE retinopathy
  arm group label: On Hydroxychloroquine, NO retinopathy
  arm group label: On Hydroxychloroquine, POSSIBLE retinopathy
  intervention type: Diagnostic Test
  intervention name: Macular Autofluorescence (Standard of Care test)
  description: Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)
  arm group label: Normative Controls
  arm group label: On Hydroxychloroquine, DEFINITE retinopathy
  arm group label: On Hydroxychloroquine, NO retinopathy
  arm group label: On Hydroxychloroquine, POSSIBLE retinopathy
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  last name: Professor Timothy L Jackson
  role: Study Chair
  affiliation: King's College Hospital NHS Trust
  last name: Professor Timothy L Jackson
  phone: 020 3299 1297
  email: t.jackson1@nhs.net
  last name: Dr Chan Ning Lee
  phone: 020 3299 1297
  email: channing.lee2@nhs.net
  responsible party type: Sponsor
  mesh term: Retinal Diseases
  sharing ipd: Undecided