<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/NCT02232503</url>
  </required_header>
  <id_info>
    <org_study_id>CRFB002DSK01</org_study_id>
    <nct_id>NCT02232503</nct_id>
  </id_info>
  <brief_title>Prevalence of DIAbetic RETinopathy and Impact of Genetic Factors in the Development of Diabetic Retinopathy of Patients With Type 1 and 2 Diabetes Mellitus in SlovaKia</brief_title>
  <acronym>DIARET SK</acronym>
  <official_title>DIARET SK - Prevalence of Diabetic Retinopathy and Impact of Genetic Factors in the Development of Diabetic Retinopathy of Patients With Type 1 and 2 Diabetes Mellitus in Slovakia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Slovakia, s.r.o.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medirex Group Academy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Slovak Technical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Comenius University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to find out prevalence and individual stages of Diabetic Retinopathy&#xD;
      in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements&#xD;
      in Slovak Republic. The outcome of the project will be epidemiology survey, prevalence of&#xD;
      diabetic retinopathy (DR) and diabetic macular edema (DME) in relation to type and duration&#xD;
      of diabetes mellitus and risk factors. Project will also identify genetic factors linked with&#xD;
      the diseases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The prevalence of diabetic retinopathy as the proportion of patients with DR (any stage) in a given subgroup according to DM duration</measure>
    <time_frame>participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria</time_frame>
    <description>The results will be accompanied by Wald 95% confidence intervals. The combined prevalence results from more subgroups will be evaluated using weighted average using the best available epidemiology data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the prevalence and individual stages of Diabetic Retinopathy in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements</measure>
    <time_frame>participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria</time_frame>
    <description>The calculation of prevalence for each stage of DR will be analyzed using the same methods as for the total DR prevalence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the prevalence and individual stages of Diabetic Macular Edema (DME) in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements</measure>
    <time_frame>participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria</time_frame>
    <description>The calculation of prevalence for each stage of DME will be analyzed using the same methods as for the total DR prevalence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the impact of risk factors on the prevalence of Diabetic Retinopathy and Diabetic Macular Edema</measure>
    <time_frame>participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria</time_frame>
    <description>The analysis will be realized using multivariate logistics regression. The output of the analysis will be the impact statistical significance of the individual risk factors represented by odds ratio for each risk parameter accompanied with statistical significance and corresponding confidence interval. The risk factors will be at least: age, gender, ethnicity, DM duration since diagnosis, glycemic control and diabetes management based on the average HbA1c of all measurements in the last 12 months, presence of nephropathy, malignancies and BMI.&#xD;
Age, DM duration since diagnosis, diabetes control based on the average HbA1c of all measurements in the last 12 months and BMI will be assessed as continuous covariates whereas gender, nationality, presence of nephropathy and malignancies will be considered as categorical variables.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Epidemiological characteristics of patients with Diabetes Mellitus and with Diabetic Retinopathy in terms of demographic structure, treatment and control of DM and the presence of other microvascular and ophthalmologic complications</measure>
    <time_frame>participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria</time_frame>
    <description>The patient characteristics will be described as by standard methods of descriptive statistics - N, %, mean, media, min, max, SD and where necessary accompanied by the histogram or contingence table.</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluate the impact of diabetic retinopathy and diabetes mellitus on the Quality Of Life as measured by NEI-VFQ25 questionnaires</measure>
    <time_frame>participants examined each working day within selected working hours during a 6 months period in selected ophthalmology centers according to protocol criteria</time_frame>
    <description>The impact of DR and DME on the quality of life in case of patients with DM will be realized using ANCOVA method where QoL will be evaluated as the continuous variable. The multivariate analysis will include all relevant patient characteristics including visual acuity, age and gender of the patient. These characteristics will serve as covariates to correct for the difference in characteristics of patient with/without DR.</description>
  </other_outcome>
  <other_outcome>
    <measure>Investigate DNA polymorphisms and phenotypic features correlating with the development of DR in patients with extreme phenotypes.</measure>
    <time_frame>DNA analysis during 7 months post study screening period</time_frame>
    <description>Genetic analysis is primarily exploratory in nature, does not test the hypothesis previously postulated and formal calculation of sample size can not be determined. In combination with accurately determined ocular and diabetic history is sample size above standard within typical publications of the topic.</description>
  </other_outcome>
  <other_outcome>
    <measure>The analysis of mitochondrial DNA haplotypes in pre-defined patient groups</measure>
    <time_frame>DNA analysis during 7 months post study screening period</time_frame>
    <description>Basic statistical analysis will include binary logistic regression (OR, 95% CI) and Fisher test. This method evaluates the statistical significance for the increase or decrease in the risk of DR for easy single nucleotide polymorphisms (SNPs) in in mitochondrial DNA (mtDNA), their combinations - DNA haplotypes, haplogroups and their clusters and thus identifies possible genetic factors involved in the study disease.</description>
  </other_outcome>
  <other_outcome>
    <measure>The identification of patients with monogenic DM by biomarkers (hsCRP)</measure>
    <time_frame>DNA analysis during 7 months post study screening period</time_frame>
    <description>Calculation of prevalence HNF1A-MODY in a wide Slovak population with diabetes using biomarker hsCRP.&#xD;
Comparison of the severity of retinopathy in mutation carriers of HNF1A-MODY and type 2 diabetes / type 1 diabetes patients in the specified data set.</description>
  </other_outcome>
  <other_outcome>
    <measure>Identification of patients with extreme phenotypes and family history of DM with eye complications</measure>
    <time_frame>DNA analysis during 7 months post study screening period</time_frame>
  </other_outcome>
  <enrollment type="Actual">4011</enrollment>
  <condition>Diabetic Retinopathy</condition>
  <condition>Diabetic Macular Edema</condition>
  <condition>Diabetes Mellitus</condition>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Studied cohort</intervention_name>
    <description>For the purpose of DNA isolation prior to genetic analysis of patients two samples of peripheral blood will be taken; first in the volume of 3.5 ml and second in the volume of 9 ml from each patient included into the study.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      For the purpose of DNA isolation prior to genetic analysis two samples of peripheral blood&#xD;
      will be taken. Tubes with sampled material will be stored under temperature of 2 - 8°C and in&#xD;
      the least possible time delivered to the laboratory where DNA will be isolated. Of all the&#xD;
      samples delivered to the laboratory, DNA will be extracted using the automated isolation&#xD;
      method. From the second sample related to the genetic analysis also the plasma will be&#xD;
      obtained and stored at -20°C. The DNA sample is then divided into two aliquot parts which&#xD;
      will be stored separately for future analysis in order to decrease the risk of their&#xD;
      impairment. DNA isolated from cells of biological material will be properly stored prior to&#xD;
      further analysis. DNA will be archived by its freezing to -80°C, a temperature in which the&#xD;
      characteristics are maintained for several decades.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Total expected number of patients included in this survey is 5000. With the objective to&#xD;
        guarantee non-biased patient selection sample, each screening day the pre-specified&#xD;
        sequence of patients (5th, 10th, 15th...) will selected. If the pre-selected patient does&#xD;
        not come for visit or does not fulfill the inclusion criteria or does not want to sign the&#xD;
        informed consent the next patient is asked to participate in the research. We plan to&#xD;
        enroll 4500 patients using this non-biased method.&#xD;
&#xD;
        The weakness of the non-biased random selection is that the less frequent groups of&#xD;
        patients will not have enough subjects for the proper statistical analysis. To correct for&#xD;
        this effect pool of 500 patients is reserved for special subgroups. Pre-defined subgroups&#xD;
        are:&#xD;
&#xD;
          1. patients with DM duration more 20 years&#xD;
&#xD;
          2. patients with DM duration less than 5 years already with DR in history All patients&#xD;
             from these subgroups will be asked to participate in this project regardless of the&#xD;
             pre-specified order.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Signed informed consent for epidemiological research&#xD;
&#xD;
          -  Signed informed consent for genetic research&#xD;
&#xD;
          -  Patients with DM - type I and II regardless of the DM duration&#xD;
&#xD;
          -  All DM patients must be included regardless of presence of eye complications in&#xD;
             patient´s anamnesis or during the examination by the diabetologist Subgroups analysis&#xD;
&#xD;
          -  Patients with DM - type I and II and DM duration ≥ 20 years&#xD;
&#xD;
          -  Patients with DM - type I and II and DM duration &lt; 5 years and DR in history&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age at the time of inclusion into the &lt;18 years&#xD;
&#xD;
          -  Gestational DM or secondary-induced diabetes&#xD;
&#xD;
          -  Diabetic ketoacidosis or hyperosmolar coma&#xD;
&#xD;
          -  Alcohol abuse or acute alcohol intoxication&#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>Dagmar Buckova, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Carnogursky, MSc.</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Svetlana Sefcikova, MD</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pavol Tison, MD</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Iveta Tvrda, MD</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniela Gasperikova, MSc., PhD.</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ivana Hojsikova, RNDr.</last_name>
    <role>Study Director</role>
    <affiliation>Medirex Group Academy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ludevit Kadasi, RNDr., DrSc.</last_name>
    <role>Study Director</role>
    <affiliation>Comenius University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Iwar Klimes, Prof., MD, DrSc.</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Slovakia, s.r.o.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Jackuliak, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Bratislava</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vladimir Krasnik, MD PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Bratislava</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emil Martinka, MD, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute for Endocrinology and Diabetology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marian Mokan, Prof. MD DrSc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jesenius University Martin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zuzana Nemethyova, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Diabetology Dispensary Bratislava</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marta Ondrejkova, MD PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>F.D. Roosevelt Hospital Banska Bystrica</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jana Stefanickova, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Bratislava</affiliation>
  </overall_official>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>September 21, 2016</last_update_submitted>
  <last_update_submitted_qc>September 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
    <mesh_term>Diabetes Mellitus</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/NCT02232503
org study id: CRFB002DSK01
nct id: NCT02232503
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The aim of the study is to find out prevalence and individual stages of Diabetic Retinopathy
      in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements
      in Slovak Republic. The outcome of the project will be epidemiology survey, prevalence of
      diabetic retinopathy (DR) and diabetic macular edema (DME) in relation to type and duration
      of diabetes mellitus and risk factors. Project will also identify genetic factors linked with
      the diseases.
time perspective: Cross-Sectional
measure: The prevalence of diabetic retinopathy as the proportion of patients with DR (any stage) in a given subgroup according to DM duration
time frame: participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria
description: The results will be accompanied by Wald 95% confidence intervals. The combined prevalence results from more subgroups will be evaluated using weighted average using the best available epidemiology data.
measure: Evaluate the prevalence and individual stages of Diabetic Retinopathy in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements
time frame: participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria
description: The calculation of prevalence for each stage of DR will be analyzed using the same methods as for the total DR prevalence.
measure: Evaluate the prevalence and individual stages of Diabetic Macular Edema (DME) in patients with type 1 and type 2 DM verified based on complex ophthalmologic measurements
time frame: participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria
description: The calculation of prevalence for each stage of DME will be analyzed using the same methods as for the total DR prevalence
measure: Evaluate the impact of risk factors on the prevalence of Diabetic Retinopathy and Diabetic Macular Edema
time frame: participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria
description: The analysis will be realized using multivariate logistics regression. The output of the analysis will be the impact statistical significance of the individual risk factors represented by odds ratio for each risk parameter accompanied with statistical significance and corresponding confidence interval. The risk factors will be at least: age, gender, ethnicity, DM duration since diagnosis, glycemic control and diabetes management based on the average HbA1c of all measurements in the last 12 months, presence of nephropathy, malignancies and BMI.
Age, DM duration since diagnosis, diabetes control based on the average HbA1c of all measurements in the last 12 months and BMI will be assessed as continuous covariates whereas gender, nationality, presence of nephropathy and malignancies will be considered as categorical variables.
measure: Epidemiological characteristics of patients with Diabetes Mellitus and with Diabetic Retinopathy in terms of demographic structure, treatment and control of DM and the presence of other microvascular and ophthalmologic complications
time frame: participants screened each working day within 8 working hours during a 6 months period in selected diabetology centers according to protocol criteria
description: The patient characteristics will be described as by standard methods of descriptive statistics - N, %, mean, media, min, max, SD and where necessary accompanied by the histogram or contingence table.
measure: Evaluate the impact of diabetic retinopathy and diabetes mellitus on the Quality Of Life as measured by NEI-VFQ25 questionnaires
time frame: participants examined each working day within selected working hours during a 6 months period in selected ophthalmology centers according to protocol criteria
description: The impact of DR and DME on the quality of life in case of patients with DM will be realized using ANCOVA method where QoL will be evaluated as the continuous variable. The multivariate analysis will include all relevant patient characteristics including visual acuity, age and gender of the patient. These characteristics will serve as covariates to correct for the difference in characteristics of patient with/without DR.
measure: Investigate DNA polymorphisms and phenotypic features correlating with the development of DR in patients with extreme phenotypes.
time frame: DNA analysis during 7 months post study screening period
description: Genetic analysis is primarily exploratory in nature, does not test the hypothesis previously postulated and formal calculation of sample size can not be determined. In combination with accurately determined ocular and diabetic history is sample size above standard within typical publications of the topic.
measure: The analysis of mitochondrial DNA haplotypes in pre-defined patient groups
time frame: DNA analysis during 7 months post study screening period
description: Basic statistical analysis will include binary logistic regression (OR, 95% CI) and Fisher test. This method evaluates the statistical significance for the increase or decrease in the risk of DR for easy single nucleotide polymorphisms (SNPs) in in mitochondrial DNA (mtDNA), their combinations - DNA haplotypes, haplogroups and their clusters and thus identifies possible genetic factors involved in the study disease.
measure: The identification of patients with monogenic DM by biomarkers (hsCRP)
time frame: DNA analysis during 7 months post study screening period
description: Calculation of prevalence HNF1A-MODY in a wide Slovak population with diabetes using biomarker hsCRP.
Comparison of the severity of retinopathy in mutation carriers of HNF1A-MODY and type 2 diabetes / type 1 diabetes patients in the specified data set.
measure: Identification of patients with extreme phenotypes and family history of DM with eye complications
time frame: DNA analysis during 7 months post study screening period
intervention type: Genetic
intervention name: Studied cohort
description: For the purpose of DNA isolation prior to genetic analysis of patients two samples of peripheral blood will be taken; first in the volume of 3.5 ml and second in the volume of 9 ml from each patient included into the study.
For the purpose of DNA isolation prior to genetic analysis two samples of peripheral blood
      will be taken. Tubes with sampled material will be stored under temperature of 2 - 8°C and in
      the least possible time delivered to the laboratory where DNA will be isolated. Of all the
      samples delivered to the laboratory, DNA will be extracted using the automated isolation
      method. From the second sample related to the genetic analysis also the plasma will be
      obtained and stored at -20°C. The DNA sample is then divided into two aliquot parts which
      will be stored separately for future analysis in order to decrease the risk of their
      impairment. DNA isolated from cells of biological material will be properly stored prior to
      further analysis. DNA will be archived by its freezing to -80°C, a temperature in which the
      characteristics are maintained for several decades.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dagmar Buckova, M.D.
role: Study Director
affiliation: Novartis Slovakia
last name: Peter Carnogursky, MSc.
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Svetlana Sefcikova, MD
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Pavol Tison, MD
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Iveta Tvrda, MD
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Daniela Gasperikova, MSc., PhD.
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Ivana Hojsikova, RNDr.
role: Study Director
affiliation: Medirex Group Academy
last name: Ludevit Kadasi, RNDr., DrSc.
role: Study Director
affiliation: Comenius University
last name: Iwar Klimes, Prof., MD, DrSc.
role: Study Director
affiliation: Novartis Slovakia, s.r.o.
last name: Peter Jackuliak, MD
role: Principal Investigator
affiliation: University Hospital Bratislava
last name: Vladimir Krasnik, MD PhD.
role: Principal Investigator
affiliation: University Hospital Bratislava
last name: Emil Martinka, MD, PhD.
role: Principal Investigator
affiliation: National Institute for Endocrinology and Diabetology
last name: Marian Mokan, Prof. MD DrSc.
role: Principal Investigator
affiliation: Jesenius University Martin
last name: Zuzana Nemethyova, MD
role: Principal Investigator
affiliation: Diabetology Dispensary Bratislava
last name: Marta Ondrejkova, MD PhD.
role: Principal Investigator
affiliation: F.D. Roosevelt Hospital Banska Bystrica
last name: Jana Stefanickova, MD
role: Principal Investigator
affiliation: University Hospital Bratislava
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy
mesh term: Diabetes Mellitus