<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/NCT03264976</url>
  </required_header>
  <id_info>
    <org_study_id>2017-KE-194</org_study_id>
    <nct_id>NCT03264976</nct_id>
  </id_info>
  <brief_title>Role of the Serum Exosomal miRNA in Diabetic Retinopathy (DR)</brief_title>
  <official_title>Prognostic Role of Serum Exosomal miRNA and Its Function in Pathogenesis of Diabetic Retinopathy (DR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Diabetic retinopathy (DR) is one of the most common causes of blindness worldwide. It is a&#xD;
      progressive disease and its detection in early phases is very crucial for visional outcomes.&#xD;
      miRNA of exosomes has been recently considered as a potential circulating marker of&#xD;
      oculopathy, including age-related macular degeneration and uveal melanoma. Therefore, the&#xD;
      primary objective of this study is to evaluate whether the serum exosomal miRNA could be&#xD;
      prospective prognosis biomarker to investigate the initiation and development of DR. This&#xD;
      case-control study is planned to include diabetic patients, and patients without DR, which&#xD;
      serve as controls. Other participants will be divided into four groups by different DR stages&#xD;
      according to the guideline from AAO. Information and samples of all trial participants will&#xD;
      be collected at the inception of the study, including basic information, medical history,&#xD;
      serum samples, and several ophthalmologic examinations. Then these information and&#xD;
      examinations will be collected at regular intervals: every 12 months until 5 years. Different&#xD;
      statistical methods will be used to identify significant associations between DR progression&#xD;
      and different exosomal miRNA. We hypothesis that there could exist alert level of exosomal&#xD;
      miRNAs which indicate the onset and development of DR in diabetic patients. Moreover, the&#xD;
      selected exosomal miRNAs, being considered together with other information including medical&#xD;
      history, blood indicators and ophthalmologic examinations, to be chosen-optimized as a&#xD;
      prognostic model for DR, which may help predicting high risk groups of DR and those with poor&#xD;
      prognosis. Based on clinical trial data, we will further discuss about possible roles of&#xD;
      identified miRNA of exosomes in the pathogenesis of DR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</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>exosomal miRNAs in serum samples</measure>
    <time_frame>samples will be collected every 12 months later until 5 years</time_frame>
    <description>In discovery set, miRNA sequencing of serum exosomes will be performed for each sample. Data will be analyzed using statistical methods. Potential miRNAs that show group-differentiation will be selected in combination with information and test results.Based on these selected miRNAs, the same assays will be repeated on all validation set samples to screen out significant miRNA.</description>
  </primary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Diabetic Retinopathy</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <description>Patients without DR. Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <description>Patients with mild non-proliferative DR (NPDR). Diagnosed according to Diabetic retinopathy PPP - Updated 2016.&#xD;
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <description>Patients with moderate NPDR. Diagnosed according to Diabetic retinopathy PPP - Updated 2016.&#xD;
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination.These information and examinations will be collected at regular intervals: every 12 months until 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <description>Patients with moderate NPDR. Diagnosed according to Diabetic retinopathy PPP - Updated 2016.&#xD;
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <description>Proliferative DR (PDR). Diagnosed according to Diabetic retinopathy PPP - Updated 2016.&#xD;
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination.These information and examinations will be collected at regular intervals: every 12 months until 5 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>hematological examination, ophthalmic examination</intervention_name>
    <description>Hematological examination includes biochemical examination, routine coagulation test, HbA1c, C reactive protein (CRP)；Ophthalmic examination includes the basic situation and clinical diagnosis of eyes, ETDRS visual acuity chart score, intraocular pressure, OCT examination, OCTA examination, fundus photos, Optos wide angle fundus imaging.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      5ml serum will be obtained from each participant.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be chosen according to the inclusion and exclusion standard and written&#xD;
        informed consent will be obtained from all participants.&#xD;
&#xD;
        Exit criteria： During the research, for his / her own consideration or at the request of&#xD;
        the investigator the patient may withdraw from the trial at any time. For each subject who&#xD;
        withdrew from the trial, the investigator must detail the subject's exit date, the reason,&#xD;
        and other information in case report form（CRF）.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type II diabetics,&#xD;
&#xD;
          -  Age &gt; 18 years old,&#xD;
&#xD;
          -  Have not accepted anti-VEGF therapy,&#xD;
&#xD;
          -  Without turbid ocular media or corestenoma that interfere with ophthalmic fundus&#xD;
             examination (patients with PDR are excluded).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Patients with any following eye disease in studied eye:&#xD;
&#xD;
          1. active infections (i.e., blepharitis, keratitis, scleritis, conjunctivitis, etc.),&#xD;
&#xD;
          2. fundus oculi diseases other than DR (i.e., retinal vein occlusion, choroidal&#xD;
             neovascularization, retinal detachment, macular hole, vitreous traction in macular&#xD;
             region, epiretinal membrane, etc.) ,&#xD;
&#xD;
          3. uncontrollable glaucoma (intraocular pressure is no less than 25mmHg after&#xD;
             anti-glaucoma agents) or after filtering surgery for glaucoma;&#xD;
&#xD;
             -Patients who have accepted any following treatment in studied eyes:&#xD;
&#xD;
          4. intraocular injection of corticosteroids (i.e., Triamcinolone) within 3 months, or&#xD;
             peribulbar injection of corticosteroids within 1 months,&#xD;
&#xD;
          5. vitrectomy surgery,&#xD;
&#xD;
          6. anti-VEGF therapy for eyes or other parts of the body (i.e., ranibizumab, bevacizumab,&#xD;
             conbercept, aflibercept, pegaptanib sodium, etc),&#xD;
&#xD;
          7. any intraocular surgery within 3 months (i.e., cataract surgery, YAG laser&#xD;
             capsulectomy, etc),&#xD;
&#xD;
          8. ocular surgery related with macular region;&#xD;
&#xD;
             -Patients with any following systemic diseases:&#xD;
&#xD;
          9. failed blood sugar control within 3 months (Changing treatment from oral antidiabetic&#xD;
             therapy into insulin treatment, or start using insulin pump, or doubling the number of&#xD;
             injections),&#xD;
&#xD;
         10. damaged renal function (Crea is found to be 2 times higher than the upper limit in&#xD;
             central laboratory) or abnormal liver function (ALT, AST are found to be 2 times&#xD;
             higher than the upper limit in center of the laboratory),&#xD;
&#xD;
         11. failed blood pressure control within 3 months (systolic blood pressure is no less than&#xD;
             140 mmHg or diastolic blood pressure is no less than 90 mmHg after hypotensor&#xD;
             treatment),&#xD;
&#xD;
         12. systemic infection that requires oral, intramuscular or intravenous administration,&#xD;
&#xD;
         13. stroke, transient ischemic attack, myocardial infarction or acute congestive heart&#xD;
             failure within 6months,&#xD;
&#xD;
         14. coagulation dysfunction (thrombin time ≥ normal upper limit of 3 seconds, activation&#xD;
             of partial thromboplastin time ≥ normal upper limit of 10 seconds),&#xD;
&#xD;
         15. using drugs that may be toxic to the lens, retina or optic nerve during this research&#xD;
             (i.e., deferoxamine, chloroquine, hydrogenated chloroquine (chloroquinol), tamoxifen,&#xD;
             phenothiazine, or ethambutol, etc.),&#xD;
&#xD;
         16. diagnosed systemic immune diseases (i.e., mandatory spondylitis, systemic lupus&#xD;
             erythematosus, etc.) or any uncontrollable clinical diseases (such as AIDS,&#xD;
             malignancy, active hepatitis, severe mental, neurological, cardiovascular, respiratory&#xD;
             and other systems diseases, etc.);&#xD;
&#xD;
             -Others:&#xD;
&#xD;
         17. pregnant and lactating women,&#xD;
&#xD;
         18. those who participated in any drug clinical trials (not including vitamins and&#xD;
             minerals) within 3 months,&#xD;
&#xD;
         19. those researchers believe that need to be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 25, 2017</last_update_submitted>
  <last_update_submitted_qc>August 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Kun Liu</investigator_full_name>
    <investigator_title>Chief Physician</investigator_title>
  </responsible_party>
  <keyword>diabetic retinopathy</keyword>
  <keyword>miRNA</keyword>
  <keyword>serum exosomes</keyword>
  <keyword>prognostic biomarker</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>
  </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/NCT03264976
org study id: 2017-KE-194
nct id: NCT03264976
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Diabetic retinopathy (DR) is one of the most common causes of blindness worldwide. It is a
      progressive disease and its detection in early phases is very crucial for visional outcomes.
      miRNA of exosomes has been recently considered as a potential circulating marker of
      oculopathy, including age-related macular degeneration and uveal melanoma. Therefore, the
      primary objective of this study is to evaluate whether the serum exosomal miRNA could be
      prospective prognosis biomarker to investigate the initiation and development of DR. This
      case-control study is planned to include diabetic patients, and patients without DR, which
      serve as controls. Other participants will be divided into four groups by different DR stages
      according to the guideline from AAO. Information and samples of all trial participants will
      be collected at the inception of the study, including basic information, medical history,
      serum samples, and several ophthalmologic examinations. Then these information and
      examinations will be collected at regular intervals: every 12 months until 5 years. Different
      statistical methods will be used to identify significant associations between DR progression
      and different exosomal miRNA. We hypothesis that there could exist alert level of exosomal
      miRNAs which indicate the onset and development of DR in diabetic patients. Moreover, the
      selected exosomal miRNAs, being considered together with other information including medical
      history, blood indicators and ophthalmologic examinations, to be chosen-optimized as a
      prognostic model for DR, which may help predicting high risk groups of DR and those with poor
      prognosis. Based on clinical trial data, we will further discuss about possible roles of
      identified miRNA of exosomes in the pathogenesis of DR.
observational model: Case-Control
time perspective: Prospective
measure: exosomal miRNAs in serum samples
time frame: samples will be collected every 12 months later until 5 years
description: In discovery set, miRNA sequencing of serum exosomes will be performed for each sample. Data will be analyzed using statistical methods. Potential miRNAs that show group-differentiation will be selected in combination with information and test results.Based on these selected miRNAs, the same assays will be repeated on all validation set samples to screen out significant miRNA.
arm group label: Group 1
description: Patients without DR. Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.
arm group label: Group 2
description: Patients with mild non-proliferative DR (NPDR). Diagnosed according to Diabetic retinopathy PPP - Updated 2016.
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.
arm group label: Group 3
description: Patients with moderate NPDR. Diagnosed according to Diabetic retinopathy PPP - Updated 2016.
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination.These information and examinations will be collected at regular intervals: every 12 months until 5 years.
arm group label: Group 4
description: Patients with moderate NPDR. Diagnosed according to Diabetic retinopathy PPP - Updated 2016.
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination. These information and examinations will be collected at regular intervals: every 12 months until 5 years.
arm group label: Group 5
description: Proliferative DR (PDR). Diagnosed according to Diabetic retinopathy PPP - Updated 2016.
Information and samples of all trial participants at enrollment will be collected at the inception of the study, including: basic information, basic medical records, hematological examination, ophthalmic examination.These information and examinations will be collected at regular intervals: every 12 months until 5 years.
intervention type: Diagnostic Test
intervention name: hematological examination, ophthalmic examination
description: Hematological examination includes biochemical examination, routine coagulation test, HbA1c, C reactive protein (CRP)；Ophthalmic examination includes the basic situation and clinical diagnosis of eyes, ETDRS visual acuity chart score, intraocular pressure, OCT examination, OCTA examination, fundus photos, Optos wide angle fundus imaging.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
arm group label: Group 5
5ml serum will be obtained from each participant.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
investigator full name: Kun Liu
investigator title: Chief Physician
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy