<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/NCT03821753</url>
  </required_header>
  <id_info>
    <org_study_id>K170406J</org_study_id>
    <nct_id>NCT03821753</nct_id>
  </id_info>
  <brief_title>The Effect of the Glycemic Variability on Macular Retinal Microcirculation and Cognitive Functions in Patient With Type 1 Diabetes</brief_title>
  <acronym>REVADIAB</acronym>
  <official_title>The Effect of the Glycemic Variability on Macular Retinal Microcirculation and Cognitive Functions in Patient With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Délégation de la Recherche Clinique et de l'innovation (DRCI)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>CRC (Centre de Recherche Clinique)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>SFD (Société Francophone du Diabète)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Revadiab is case-control study aimed to demonstrate that retinal capillary density is altered&#xD;
      in patients with type 1 diabetes with glycemic variability compared to those with comparable&#xD;
      glycemic control without glycemic variability. An OCT angiography will be used to precisely&#xD;
      evaluate retinal capillary density.&#xD;
&#xD;
      A secondary objective will be to evaluate if glycemic variability is associated with&#xD;
      cognitive dysfunction, using a neuro psychologic evaluation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HbA1c doesn't explain all the microvascular complications of diabetes, especially&#xD;
      microvascular complications. Glycemic variability is associated with increased oxidative&#xD;
      stress, free radicals and endothelial dysfunction; it contributes to the pathogenesis of&#xD;
      diabetic complications.&#xD;
&#xD;
      The relationship between glycemic variability and microangiopathic complications especially&#xD;
      retinal but also neurological, needs to be studied.&#xD;
&#xD;
      The principal objective of Revadiab study is to demonstrate a correlation between glycemic&#xD;
      variability and macular retinal microcirculation in patient with type 1 diabetes.&#xD;
&#xD;
      The secondary objective is to search a correlation between glycemic variability and :&#xD;
&#xD;
        -  Alteration of cognitive functions.&#xD;
&#xD;
        -  Severity of peripheral diabetic retinopathy and retinal neuronal damage.&#xD;
&#xD;
        -  Other micro and macro angiopathic complications.&#xD;
&#xD;
        -  Oxidative stress and inflammation.&#xD;
&#xD;
      Two groups of type 1 diabetic patients will be compared:&#xD;
&#xD;
        -  Case: Patient with significant glycemic variability.&#xD;
&#xD;
        -  Control: Patients without glycemic variability.&#xD;
&#xD;
      The severity of diabetic retinopathy will be evaluated by the degree of occlusion of small&#xD;
      vessels in the central retinal region as measured by OCT angiography.&#xD;
&#xD;
      Acts or Product necessary to research :&#xD;
&#xD;
        -  Non-invasive retinal imaging (OCT and OCT- Angiography, retinophotography)&#xD;
&#xD;
        -  Neuropsychological tests.&#xD;
&#xD;
        -  Blood test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2020</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Macular capillary density in the external deep capillary network</measure>
    <time_frame>3 months</time_frame>
    <description>Macular capillary density in the external deep capillary network measured by OCT-Angiography (no later than 3 months after inclusion)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Macular capillary density in the deep capillary and deep capillary network</measure>
    <time_frame>3 months</time_frame>
    <description>Macular capillary density in the deep capillary and deep capillary network measured by OCT-angiography (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area of the central avascular zone</measure>
    <time_frame>3 months</time_frame>
    <description>Area of the central avascular zone by OCT-Angiography (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macular edema presence</measure>
    <time_frame>3 months</time_frame>
    <description>Macular edema presence by OCT (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Layer thickness reduction of the ganglion cells</measure>
    <time_frame>3 months</time_frame>
    <description>Layer thickness reduction of the ganglion cells measured by OCT (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetic retinopathy stage</measure>
    <time_frame>3 months</time_frame>
    <description>Diabetic retinopathy stage evaluated with retinographies (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of pre-retinal neovascular vessels and/or pre-papillary</measure>
    <time_frame>3 months</time_frame>
    <description>Development of pre-retinal neovascular vessels and/or pre-papillary (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of neovascular complications</measure>
    <time_frame>3 months</time_frame>
    <description>Occurrence of neovascular complications: vitreous</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Haemorrhage, retina tractional detachment, neovascular glaucoma</measure>
    <time_frame>3 months</time_frame>
    <description>Haemorrhage, retina tractional detachment, neovascular glaucoma (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function evaluation</measure>
    <time_frame>3 months</time_frame>
    <description>Renal function evaluation: microalbuminuria and creatinine determination (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of peripheral neuropathy</measure>
    <time_frame>3 months</time_frame>
    <description>Evaluation of peripheral neuropathy : monofilament test (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic cardiopathy</measure>
    <time_frame>3 months</time_frame>
    <description>Measurement method: treatment with angioplasty or coronary artery bypass graft, Assessment of vascular risk by measuring the coronal calcium score, and determination of BNP and troponin. (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of severe hypoglycemia</measure>
    <time_frame>3 months</time_frame>
    <description>Number of severe hypoglycemia since 1 year, threshold for hypoglycemia no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of inflammation</measure>
    <time_frame>3 months</time_frame>
    <description>characterization of circulating inflammatory and endothelial cells and CRP-US assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress markers</measure>
    <time_frame>3 months</time_frame>
    <description>Oxidative stress markers: Measurements of 8-iso-prostaglandin F2 alpha urinary and 1,5-anhydroglucitol sanguine. (no later than 3 months after inclusion)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Microvascular Complications</condition>
  <condition>Diabetic Retinopathy</condition>
  <condition>Diabetes</condition>
  <condition>Microangiopathy</condition>
  <condition>Angiography</condition>
  <arm_group>
    <arm_group_label>Case</arm_group_label>
    <description>Patients with glycemic variability, defined by a coefficient of variation (CV)&gt; 36%, calculated from continuous glucose measurements data by Free Style Libre® (Abbott)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Patients without glycemic variability, defined by a coefficient of variation (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for HbA1c (+/- 0.5%)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Case</intervention_name>
    <description>OCT&#xD;
OCT-Angiography,&#xD;
Retinophotography&#xD;
Neuropsychological tests</description>
    <arm_group_label>Case</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>OCT&#xD;
OCT-Angiography,&#xD;
Retinophotography&#xD;
Neuropsychological tests</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Inclusion of adult patients with T1D with more than 10 years of diabetes and users of the&#xD;
        FreeStyle Free continuous measurement system.&#xD;
&#xD;
        Case: Patients with glycemic variability, defined by a coefficient of variation (CV) &gt; 36%,&#xD;
        calculated from continuous glucose measurements data by Free Style Libre® (Abbott).&#xD;
&#xD;
        Controls: Patients without glycemic variability, defined by a coefficient of variation (CV)&#xD;
        ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for&#xD;
        HbA1c (+/- 0.5%).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥ 18 years&#xD;
&#xD;
          -  Type 1 diabetes (T1D)&#xD;
&#xD;
          -  Using Free FreeStyle&#xD;
&#xD;
          -  Diabete evolving for 10 years or more&#xD;
&#xD;
          -  Case: Patients with glycemic variability, defined by a coefficient of variation (CV) &gt;&#xD;
             36%, calculated from continuous glucose measurements data by Free Style Libre®&#xD;
             (Abbott)&#xD;
&#xD;
          -  Controls: Patients without glycemic variability, defined by a coefficient of variation&#xD;
             (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case&#xD;
             group for HbA1c (+/- 0.5%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetic patient&#xD;
&#xD;
          -  Corticotherapy&#xD;
&#xD;
          -  Comorbidity like cancer&#xD;
&#xD;
          -  Antecedent of vitreoretinal pathology&#xD;
&#xD;
          -  Antecedent of vitreoretinal surgery&#xD;
&#xD;
          -  Important cataract, with an important opacity that prevents a reliable evaluation of&#xD;
             capillary density in OCT angio&#xD;
&#xD;
          -  Pregnant or lactating woman&#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_contact>
    <last_name>Jean Pierre RIVELINE, Professor</last_name>
    <phone>+33(0) 1 49 95 83 79</phone>
    <email>jeanpierre.riveline@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <state>Ile-de-France</state>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Pierre RIVELINE, Professor</last_name>
      <phone>+33(0) 1 49 95 83 79</phone>
      <email>jeanpierre.riveline@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>January 25, 2019</last_update_submitted>
  <last_update_submitted_qc>January 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetic retinopathy</keyword>
  <keyword>Glycemic variability</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Macular retinal microcirculation</keyword>
  <keyword>Microangiopathy</keyword>
  <keyword>Cognitive dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_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/NCT03821753
org study id: K170406J
nct id: NCT03821753
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Revadiab is case-control study aimed to demonstrate that retinal capillary density is altered
      in patients with type 1 diabetes with glycemic variability compared to those with comparable
      glycemic control without glycemic variability. An OCT angiography will be used to precisely
      evaluate retinal capillary density.

      A secondary objective will be to evaluate if glycemic variability is associated with
      cognitive dysfunction, using a neuro psychologic evaluation.
HbA1c doesn't explain all the microvascular complications of diabetes, especially
      microvascular complications. Glycemic variability is associated with increased oxidative
      stress, free radicals and endothelial dysfunction; it contributes to the pathogenesis of
      diabetic complications.

      The relationship between glycemic variability and microangiopathic complications especially
      retinal but also neurological, needs to be studied.

      The principal objective of Revadiab study is to demonstrate a correlation between glycemic
      variability and macular retinal microcirculation in patient with type 1 diabetes.

      The secondary objective is to search a correlation between glycemic variability and :

        -  Alteration of cognitive functions.

        -  Severity of peripheral diabetic retinopathy and retinal neuronal damage.

        -  Other micro and macro angiopathic complications.

        -  Oxidative stress and inflammation.

      Two groups of type 1 diabetic patients will be compared:

        -  Case: Patient with significant glycemic variability.

        -  Control: Patients without glycemic variability.

      The severity of diabetic retinopathy will be evaluated by the degree of occlusion of small
      vessels in the central retinal region as measured by OCT angiography.

      Acts or Product necessary to research :

        -  Non-invasive retinal imaging (OCT and OCT- Angiography, retinophotography)

        -  Neuropsychological tests.

        -  Blood test.
observational model: Case-Control
time perspective: Retrospective
measure: Macular capillary density in the external deep capillary network
time frame: 3 months
description: Macular capillary density in the external deep capillary network measured by OCT-Angiography (no later than 3 months after inclusion)
measure: Macular capillary density in the deep capillary and deep capillary network
time frame: 3 months
description: Macular capillary density in the deep capillary and deep capillary network measured by OCT-angiography (no later than 3 months after inclusion)
measure: Area of the central avascular zone
time frame: 3 months
description: Area of the central avascular zone by OCT-Angiography (no later than 3 months after inclusion)
measure: Macular edema presence
time frame: 3 months
description: Macular edema presence by OCT (no later than 3 months after inclusion)
measure: Layer thickness reduction of the ganglion cells
time frame: 3 months
description: Layer thickness reduction of the ganglion cells measured by OCT (no later than 3 months after inclusion)
measure: Diabetic retinopathy stage
time frame: 3 months
description: Diabetic retinopathy stage evaluated with retinographies (no later than 3 months after inclusion)
measure: Development of pre-retinal neovascular vessels and/or pre-papillary
time frame: 3 months
description: Development of pre-retinal neovascular vessels and/or pre-papillary (no later than 3 months after inclusion)
measure: Occurrence of neovascular complications
time frame: 3 months
description: Occurrence of neovascular complications: vitreous
measure: Haemorrhage, retina tractional detachment, neovascular glaucoma
time frame: 3 months
description: Haemorrhage, retina tractional detachment, neovascular glaucoma (no later than 3 months after inclusion)
measure: Renal function evaluation
time frame: 3 months
description: Renal function evaluation: microalbuminuria and creatinine determination (no later than 3 months after inclusion)
measure: Evaluation of peripheral neuropathy
time frame: 3 months
description: Evaluation of peripheral neuropathy : monofilament test (no later than 3 months after inclusion)
measure: Ischemic cardiopathy
time frame: 3 months
description: Measurement method: treatment with angioplasty or coronary artery bypass graft, Assessment of vascular risk by measuring the coronal calcium score, and determination of BNP and troponin. (no later than 3 months after inclusion)
measure: Number of severe hypoglycemia
time frame: 3 months
description: Number of severe hypoglycemia since 1 year, threshold for hypoglycemia no later than 3 months after inclusion)
measure: Markers of inflammation
time frame: 3 months
description: characterization of circulating inflammatory and endothelial cells and CRP-US assay
measure: Oxidative stress markers
time frame: 3 months
description: Oxidative stress markers: Measurements of 8-iso-prostaglandin F2 alpha urinary and 1,5-anhydroglucitol sanguine. (no later than 3 months after inclusion)
arm group label: Case
description: Patients with glycemic variability, defined by a coefficient of variation (CV)> 36%, calculated from continuous glucose measurements data by Free Style Libre® (Abbott)
arm group label: Control
description: Patients without glycemic variability, defined by a coefficient of variation (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for HbA1c (+/- 0.5%)
intervention type: Other
intervention name: Case
description: OCT
OCT-Angiography,
Retinophotography
Neuropsychological tests
arm group label: Case
intervention type: Other
intervention name: Control
description: OCT
OCT-Angiography,
Retinophotography
Neuropsychological tests
arm group label: Control
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean Pierre RIVELINE, Professor
phone: +33(0) 1 49 95 83 79
email: jeanpierre.riveline@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy
mesh term: Diabetes Mellitus
sharing ipd: No