<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/NCT04468152</url>
  </required_header>
  <id_info>
    <org_study_id>GO 18/562</org_study_id>
    <nct_id>NCT04468152</nct_id>
  </id_info>
  <brief_title>Advanced Glycation End Products Are Associated With Diabetic Macular Edema</brief_title>
  <official_title>Increased Dietary Intake and Serum Levels of Advanced Glycation End Products Are Associated With Diabetic Macular Edema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hacettepe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hacettepe University</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>
      Diabetic macular edema can develop at all stages of diabetic retinopathy, causing visual&#xD;
      impairment and blindness. Modern diets are high in advanced glycation end products (dAGEs),&#xD;
      derived from processing methods, exerting a pivotal role in promoting diabetic retinopathy&#xD;
      risk. In this cross-sectional study, we investigate the relationship between dietary and&#xD;
      serum levels of AGEs and DME in type 2 diabetic subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a cross-sectional study was carried out in the Hacettepe University Hospital,&#xD;
      Department of Ophthalmology, between July 2018 and February 2019.&#xD;
&#xD;
      While benefiting from the results of the previous studies, the sample size of the research&#xD;
      was type 1 error level α = 0.05 and type 2 level β = 0.20. The power analysis was&#xD;
      statistically calculated using NCCS PAS 11 program. The present study was conducted with 90&#xD;
      patients: 50 case-patients (DM with DME) and 40 control patients (DM without DME). Excluded&#xD;
      from the study were those under the age of 18 years, with no diagnosis of Type 2 DM, without&#xD;
      any anti-diabetic agent, with any disease other than DME and DR that may affect the retina,&#xD;
      with any disease that may affect the retina for the control group, with corneal, lens or&#xD;
      vitreous opacification preventing Optical coherence tomography (OCT) withdrawal, with any&#xD;
      systemic disease other than DM and hypertension, with a history of eye surgery, and with&#xD;
      blindness or infection in the eye, along with those recently diagnosed with diabetes (&lt;1&#xD;
      year) and those with special diets.&#xD;
&#xD;
      This the study was conducted in accordance with the Declaration of Helsinki Ethical&#xD;
      Principles.&#xD;
&#xD;
      OCT withdrawals and CFT evaluations of those included in the study were made by the doctor&#xD;
      and directed to the dietician (researcher). Demographic data and the dietary habits were&#xD;
      collected through standardized face-to-face interviewer-assisted questionnaires. The&#xD;
      bodyweight and height of patients were measured using a calibrated body composition analyser&#xD;
      and weight scales by researcher. BMI was evaluated based on the WHO classification. Waist and&#xD;
      hip circumference was also measured and evaluated in terms of high risk of developing chronic&#xD;
      diseases. Hypothesis: If the waist/hip ratio is ≥0.85 for women and ≥0.90 for men, the risk&#xD;
      of developing chronic diseases increases.&#xD;
&#xD;
      Diabetic macular edema (DME) Examination After a detailed systemic and ophthalmological&#xD;
      history was taken from all subjects by the doctor, the best-corrected visual acuity level was&#xD;
      measured using an ETDRS chart. A fundus examination was performed with a 90 D lens after&#xD;
      anterior segment examination and pupil dilation with a biomicroscope. A spectral-domain OCT&#xD;
      (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was applied for the evaluation&#xD;
      of CFT. After a minimum of eight hours of fasting, approximately 5 ml of peripheral venous&#xD;
      blood was collected from the antecubital region in the HÜTF Ophthalmology Clinic between&#xD;
      08:00 and 10:00.&#xD;
&#xD;
      Assessment of dietary intake and dietary AGEs The dietary intake of participants was assessed&#xD;
      using a validated quantitative food frequency questionnaire (QFFQ) (including about 110 food&#xD;
      items take 20-25 minutes to complete). Foods were classified into eight categories: dairy&#xD;
      products, meat products, fruits, vegetables, bread and cereals, beverages, and desserts.&#xD;
      Also, questions were asked to patients about traditional cooking methods to calculate dietary&#xD;
      AGE intakes. Such as what cooking methods do they cook the foods? How long do they cook the&#xD;
      food? Standardized food recipes for Turkey and the Nutrition Information System (BEBIS)&#xD;
      program were used to calculate the average daily energy and nutrient intake for each&#xD;
      participant. Meanwhile, to assess dietary AGEs from the QFFQ, each food's contribution to&#xD;
      dAGEs intake was calculated based on the Advance Glycation End Products in Foods Table&#xD;
      published by the Uribarri et al., which comprises data on 549 food items.&#xD;
&#xD;
      Sample Collection and Analysis The serum samples collected during the research were delivered&#xD;
      to the laboratory while preserving the cold chain. The enzyme-labeled immune &quot;Enzyme-Linked&#xD;
      Immunosorbent Assay (ELISA)&quot; test was performed with biologists of the company using a Biotek&#xD;
      800TS device. While analyzing the samples, Human CML Elisa Kit 96 tests for serum AGE and&#xD;
      Human RAGE Elisa Kit 96 test kits for serum RAGE were used. Carboxymethyl lysine (CML) was&#xD;
      considered as the AGE parameter, being the most easily detected and the most abundant type of&#xD;
      AGE in humans. The minimum detectable dose of CML in humans is typically less than 15.6&#xD;
      pg/ml.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 7, 2018</start_date>
  <completion_date type="Actual">January 10, 2019</completion_date>
  <primary_completion_date type="Actual">January 10, 2019</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Screening</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>We hypothesize that the AGEs levels of the DME group would found be higher than in the control group.</measure>
    <time_frame>3 months</time_frame>
    <description>The serum samples collected during the research were delivered to the laboratory while preserving the cold chain. The enzyme-labelled immune &quot;Enzyme-Linked Immunosorbent Assay (ELISA)&quot; test was performed with biologists of the company using a Biotek 800TS device. While analyzing the samples, Human CML Elisa Kit 96 tests for serum AGE is used. Carboxymethyl lysine (CML) was considered as the AGE parameter, being the most easily detected and the most abundant type of AGE in humans. The minimum detectable dose of CML in humans is typically less than 15.6 pg/ml.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>We hypothesize that the dietary intake of AGEs wolud be higher in the DME group.</measure>
    <time_frame>1 month</time_frame>
    <description>The dietary intake of participants was assessed using a validated quantitative food frequency questionnaire (QFFQ). The total food intake was then converted to total nutrient intake based on the food's nutrient profile. Standardized food recipes for Turkey and the Nutrition Information System (BEBIS) program, which is a food composition database for nutrient estimation, were used to determine the average daily energy and nutrient intake for each participant. These values were subsequently compared with the recommended daily allowance values to determine the status of meeting energy and nutrient requirements. After that, the percentages meeting the requirements were calculated. Meanwhile, to assess dietary AGEs from the QFFQ, each food's contribution to dAGEs intake was calculated based on the Advance Glycation End Products in Foods Table published by the Uribarri et al.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>We hypothesize that neck circumference correlated significantly with DME.</measure>
    <time_frame>1 month</time_frame>
    <description>The neck circumference of the participants will be measured by the researcher Sedat Arslan with a calibrated tape measure on a centimeter scale.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>We hypothesize that the sRAGE levels were higher in the DME group.</measure>
    <time_frame>3 months</time_frame>
    <description>The serum samples collected during the research were delivered to the laboratory while preserving the cold chain. The enzyme-labelled immune &quot;Enzyme-Linked Immunosorbent Assay (ELISA)&quot; test was performed with biologists of the company using a Biotek 800TS device. While analyzing the samples,Human RAGE Elisa Kit 96 test kits for serum RAGE were used.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Case</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Dietary habits and intake</intervention_name>
    <description>Optical coherence tomography (OCT) withdrawals and central foveal thickness (CFT) evaluations of those included in the study were made by the doctor and directed to the dietician (researcher). The dietary intake of participants was assessed using a validated quantitative food frequency questionnaire (QFFQ) (21). The total food intake was then converted to total nutrient intake based on the food's nutrient profile. Standardized food recipes for Turkey and the Nutrition Information System (BEBIS) program, which is a food composition database for nutrient estimation, were used to determine the average daily energy and nutrient intake for each participant.</description>
    <arm_group_label>Case</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Included from the study were those over the age of 18 years, with diagnosis of Type 2&#xD;
             DM.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Excluded from the study were those under the age of 18 years, with no diagnosis of&#xD;
             Type 2 DM, without any anti-diabetic agent, with any disease other than DME and DR&#xD;
             that may affect the retina, with any disease that may affect the retina for the&#xD;
             control group, with corneal, lens or vitreous opacification preventing Optical&#xD;
             coherence tomography (OCT) withdrawal, with any systemic disease other than DM and&#xD;
             hypertension, with a history of eye surgery, and with blindness or infection in the&#xD;
             eye, along with those recently diagnosed with diabetes (&lt;1 year) and those with&#xD;
             special diets.&#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_official>
    <last_name>Sibel Kadayıfçılar, Prof.Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Hacettepe University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gülhan Samur, Prof.Dr.</last_name>
    <role>Study Director</role>
    <affiliation>Hacettepe University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dila Kırağı, Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Hacettepe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hacettepe University Hospital Department of Ophthalmology Polyclinic</name>
      <address>
        <city>Ankara</city>
        <state>Altındağ</state>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hacettepe University</investigator_affiliation>
    <investigator_full_name>Sedat Arslan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>advanced glycation end products</keyword>
  <keyword>diabetic macular edema</keyword>
  <keyword>nutrition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Edema</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/NCT04468152
org study id: GO 18/562
nct id: NCT04468152
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Diabetic macular edema can develop at all stages of diabetic retinopathy, causing visual
      impairment and blindness. Modern diets are high in advanced glycation end products (dAGEs),
      derived from processing methods, exerting a pivotal role in promoting diabetic retinopathy
      risk. In this cross-sectional study, we investigate the relationship between dietary and
      serum levels of AGEs and DME in type 2 diabetic subjects.
This was a cross-sectional study was carried out in the Hacettepe University Hospital,
      Department of Ophthalmology, between July 2018 and February 2019.

      While benefiting from the results of the previous studies, the sample size of the research
      was type 1 error level α = 0.05 and type 2 level β = 0.20. The power analysis was
      statistically calculated using NCCS PAS 11 program. The present study was conducted with 90
      patients: 50 case-patients (DM with DME) and 40 control patients (DM without DME). Excluded
      from the study were those under the age of 18 years, with no diagnosis of Type 2 DM, without
      any anti-diabetic agent, with any disease other than DME and DR that may affect the retina,
      with any disease that may affect the retina for the control group, with corneal, lens or
      vitreous opacification preventing Optical coherence tomography (OCT) withdrawal, with any
      systemic disease other than DM and hypertension, with a history of eye surgery, and with
      blindness or infection in the eye, along with those recently diagnosed with diabetes (<1
      year) and those with special diets.

      This the study was conducted in accordance with the Declaration of Helsinki Ethical
      Principles.

      OCT withdrawals and CFT evaluations of those included in the study were made by the doctor
      and directed to the dietician (researcher). Demographic data and the dietary habits were
      collected through standardized face-to-face interviewer-assisted questionnaires. The
      bodyweight and height of patients were measured using a calibrated body composition analyser
      and weight scales by researcher. BMI was evaluated based on the WHO classification. Waist and
      hip circumference was also measured and evaluated in terms of high risk of developing chronic
      diseases. Hypothesis: If the waist/hip ratio is ≥0.85 for women and ≥0.90 for men, the risk
      of developing chronic diseases increases.

      Diabetic macular edema (DME) Examination After a detailed systemic and ophthalmological
      history was taken from all subjects by the doctor, the best-corrected visual acuity level was
      measured using an ETDRS chart. A fundus examination was performed with a 90 D lens after
      anterior segment examination and pupil dilation with a biomicroscope. A spectral-domain OCT
      (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was applied for the evaluation
      of CFT. After a minimum of eight hours of fasting, approximately 5 ml of peripheral venous
      blood was collected from the antecubital region in the HÜTF Ophthalmology Clinic between
      08:00 and 10:00.

      Assessment of dietary intake and dietary AGEs The dietary intake of participants was assessed
      using a validated quantitative food frequency questionnaire (QFFQ) (including about 110 food
      items take 20-25 minutes to complete). Foods were classified into eight categories: dairy
      products, meat products, fruits, vegetables, bread and cereals, beverages, and desserts.
      Also, questions were asked to patients about traditional cooking methods to calculate dietary
      AGE intakes. Such as what cooking methods do they cook the foods? How long do they cook the
      food? Standardized food recipes for Turkey and the Nutrition Information System (BEBIS)
      program were used to calculate the average daily energy and nutrient intake for each
      participant. Meanwhile, to assess dietary AGEs from the QFFQ, each food's contribution to
      dAGEs intake was calculated based on the Advance Glycation End Products in Foods Table
      published by the Uribarri et al., which comprises data on 549 food items.

      Sample Collection and Analysis The serum samples collected during the research were delivered
      to the laboratory while preserving the cold chain. The enzyme-labeled immune "Enzyme-Linked
      Immunosorbent Assay (ELISA)" test was performed with biologists of the company using a Biotek
      800TS device. While analyzing the samples, Human CML Elisa Kit 96 tests for serum AGE and
      Human RAGE Elisa Kit 96 test kits for serum RAGE were used. Carboxymethyl lysine (CML) was
      considered as the AGE parameter, being the most easily detected and the most abundant type of
      AGE in humans. The minimum detectable dose of CML in humans is typically less than 15.6
      pg/ml.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Screening
masking: Single (Participant)
measure: We hypothesize that the AGEs levels of the DME group would found be higher than in the control group.
time frame: 3 months
description: The serum samples collected during the research were delivered to the laboratory while preserving the cold chain. The enzyme-labelled immune "Enzyme-Linked Immunosorbent Assay (ELISA)" test was performed with biologists of the company using a Biotek 800TS device. While analyzing the samples, Human CML Elisa Kit 96 tests for serum AGE is used. Carboxymethyl lysine (CML) was considered as the AGE parameter, being the most easily detected and the most abundant type of AGE in humans. The minimum detectable dose of CML in humans is typically less than 15.6 pg/ml.
measure: We hypothesize that the dietary intake of AGEs wolud be higher in the DME group.
time frame: 1 month
description: The dietary intake of participants was assessed using a validated quantitative food frequency questionnaire (QFFQ). The total food intake was then converted to total nutrient intake based on the food's nutrient profile. Standardized food recipes for Turkey and the Nutrition Information System (BEBIS) program, which is a food composition database for nutrient estimation, were used to determine the average daily energy and nutrient intake for each participant. These values were subsequently compared with the recommended daily allowance values to determine the status of meeting energy and nutrient requirements. After that, the percentages meeting the requirements were calculated. Meanwhile, to assess dietary AGEs from the QFFQ, each food's contribution to dAGEs intake was calculated based on the Advance Glycation End Products in Foods Table published by the Uribarri et al.
measure: We hypothesize that neck circumference correlated significantly with DME.
time frame: 1 month
description: The neck circumference of the participants will be measured by the researcher Sedat Arslan with a calibrated tape measure on a centimeter scale.
measure: We hypothesize that the sRAGE levels were higher in the DME group.
time frame: 3 months
description: The serum samples collected during the research were delivered to the laboratory while preserving the cold chain. The enzyme-labelled immune "Enzyme-Linked Immunosorbent Assay (ELISA)" test was performed with biologists of the company using a Biotek 800TS device. While analyzing the samples,Human RAGE Elisa Kit 96 test kits for serum RAGE were used.
arm group label: Case
arm group type: Experimental
arm group label: Control
arm group type: No Intervention
intervention type: Behavioral
intervention name: Dietary habits and intake
description: Optical coherence tomography (OCT) withdrawals and central foveal thickness (CFT) evaluations of those included in the study were made by the doctor and directed to the dietician (researcher). The dietary intake of participants was assessed using a validated quantitative food frequency questionnaire (QFFQ) (21). The total food intake was then converted to total nutrient intake based on the food's nutrient profile. Standardized food recipes for Turkey and the Nutrition Information System (BEBIS) program, which is a food composition database for nutrient estimation, were used to determine the average daily energy and nutrient intake for each participant.
arm group label: Case
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sibel Kadayıfçılar, Prof.Dr.
role: Study Chair
affiliation: Hacettepe University
last name: Gülhan Samur, Prof.Dr.
role: Study Director
affiliation: Hacettepe University
last name: Dila Kırağı, Dr.
role: Study Chair
affiliation: Hacettepe University
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Hacettepe University
investigator full name: Sedat Arslan
investigator title: Principal Investigator
mesh term: Macular Edema
mesh term: Diabetes Mellitus, Type 2
mesh term: Edema
sharing ipd: No