<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/NCT04411277</url>
  </required_header>
  <id_info>
    <org_study_id>ADC-OUS-IIS-19-47</org_study_id>
    <nct_id>NCT04411277</nct_id>
  </id_info>
  <brief_title>Time in Range (TIR) and Time Below Range (TBR) in Insulin-Treated Elderly Patients With Type 2 Diabetes</brief_title>
  <official_title>Time in Range (TIR) and Time Below Range (TBR) in Insulin-Treated Elderly Patients With Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cline Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Abbott Diabetes Care</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cline Research Center</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>
      Prospective observational cohort study. Elderly patients &gt;65 years with type 2 diabetes&#xD;
      mellitus (T2DM) on insulin therapy and HbA1c between 7% and 9%, with or without oral agents,&#xD;
      will be identified from medical records and invited to participate. Patients will wear a&#xD;
      FreeStyle Libre Flash CGM during a 6-week study period.&#xD;
&#xD;
      Using CGM technology, we will assess an efficacy outcome : time in range (TIR) between 70-180&#xD;
      mg/dl and a safety outcome: incidence of hypoglycemia (time below range (TBR) less than 70,&#xD;
      54, and 40 mg/dl in insulin treated older adults with T2DM.&#xD;
&#xD;
      Patients will return to clinic every 2 weeks for new continuous glucose monitoring (CGM)&#xD;
      placement, assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.&#xD;
&#xD;
      CGM data will be downloaded every 2 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective observational cohort study. Patients over 65 years of age, with TDM2 using&#xD;
      insulin with or without the use of associated oral antidiabetic agents and with HbA1c between&#xD;
      7% and 9%, will be identified by medical records at the Hospital da Cruz Vermelha&#xD;
      Brasileira-Filial do Paraná and they will be invited to participate in the study by telephone&#xD;
      and forwarded to the research center Cline Research Center where the study procedures will be&#xD;
      carried out. Patients from the private clinic of neurology and endocrinology Cline will also&#xD;
      be invited by telephone. In this way the sample of patients will include patients from the&#xD;
      public and private health system.&#xD;
&#xD;
      On the first visit to the research centers, after signing the informed consent form (ICF),&#xD;
      patients will be evaluated for the presence of other comorbidities associated with diabetes&#xD;
      such as the presence of cardiovascular disease, hypertension and dyslipidemia.&#xD;
&#xD;
      The screening for the presence of sarcopenia will be performed with the application of the&#xD;
      SARC-F questionnaire; measuring muscle strength with grip strength; the functional test of&#xD;
      getting up from the chair without supporting the arms and walking for 3 meters, turning 180º&#xD;
      and returning to sit. The time in which the elderly person performs this task is timed and&#xD;
      the time up to 20 seconds is considered normal.&#xD;
&#xD;
      Patients will undergo a complete physical examination and body composition analysis using the&#xD;
      InBody 270 multifrequency bioimpedance to calculate the appendicular skeletal musculature.&#xD;
&#xD;
      After the first evaluation at the research centers, patients will be referred to partner&#xD;
      laboratories that use the same methodologies for measuring HbA1c, blood count, urea,&#xD;
      creatinine, glutamic oxalacetic transaminase (TGO) and glutamic-pyruvic transaminase (TGP),&#xD;
      which will be performed only at the initial visit.&#xD;
&#xD;
      During the second visit to the research center, the FreeStyle Libre Flash interstitial&#xD;
      glucose sensor will be inserted for the first time in the posterior and upper arm and the&#xD;
      patient will be instructed to read the glucose at least 10 times a day, being sure to check&#xD;
      glucose for a period longer than 8 hours. The patient should be instructed to return to the&#xD;
      research center every 2 weeks to change the sensor until completing the 6-week period.&#xD;
&#xD;
      The patient's travel to the research center will be reimbursed by the study team. The study&#xD;
      will be carried out at the Hospital da Cruz Vermelha Brasileira-Filial do Paraná, located in&#xD;
      Curitiba in partnership with the independent research center Cline Research Center (CRC).&#xD;
      Eligible patients will be randomly selected from clinical outpatients at participating&#xD;
      institutions, concomitantly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 5, 2020</start_date>
  <completion_date type="Actual">April 30, 2022</completion_date>
  <primary_completion_date type="Actual">April 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Primary outcome is time in range (TIR)</measure>
    <time_frame>04-07-2021</time_frame>
    <description>TIR between 70-180 mg/dL in insulin treated in patients older than 65 years.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>-Frequency of hypoglycemia (&lt;70mg/dL, &lt;54mg/dL) to measure Time Bellow Range</measure>
    <time_frame>04-07-2021</time_frame>
    <description>percentage of patients with greater than 5%-time below glucose target (&lt;70 mg/dL);&#xD;
diurnal and nocturnal hypoglycemia;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>-Time in hyperglycemia &gt; 180, 250 mg/dL to measure Time Above Range</measure>
    <time_frame>04-07-2021</time_frame>
    <description>percentage of patients with greater than 5%-time glucose above 250mg/dL&#xD;
percentage of patients with greater than 25%-time glucose above 180mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>-Adherence to CGM use and sensor utilization for diabetes care management using CGM</measure>
    <time_frame>04-07-2021</time_frame>
    <description>-assessing the percentage of captured sensor data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Rate of emergency room visits and hospitalization</measure>
    <time_frame>04-07-2021</time_frame>
    <description>-changing insulin type and dose to prevent hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>-Glucose Variability</measure>
    <time_frame>04-07-2021</time_frame>
    <description>glycemic variability standard deviation and MAGE(mean amplitude of glycemic excursions)&#xD;
glucose variability will be calculated as % coefficient of variation %CV= (standard deviation (SD)/mean glucose x 100%)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">71</enrollment>
  <condition>Continuous Glucose Monitoring</condition>
  <arm_group>
    <arm_group_label>T2DM Elderly on Insulin CGM</arm_group_label>
    <description>70 patients with type 2 diabetes &gt; 65 years of age taking insulin as treatment. The sample size was calculated to estimate the minimal number of patients necessary to describe the mean TIR (minutes/day).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Application of the FreeStyle Libre Flash Glucose CGM.</intervention_name>
    <description>Assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.</description>
    <arm_group_label>T2DM Elderly on Insulin CGM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>InBody 270 multifrequency bioimpedance</intervention_name>
    <description>analysis of body composition to calculate appendicular skeletal muscle.</description>
    <arm_group_label>T2DM Elderly on Insulin CGM</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Elderly patients &gt;65 years with T2DM on insulin therapy and HbA1c between 7% and 9%, with&#xD;
        or without oral agents, will be identified from medical records and invited to participate.&#xD;
        Patients will wear a FreeStyle Libre Flash CGM during a 6-week study period.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 65 years&#xD;
&#xD;
          -  Known history of type 2 Diabetes Mellitus&#xD;
&#xD;
          -  BMI between 18.5 and 35kg/m2&#xD;
&#xD;
          -  HbA1c between 7% and 9.0%&#xD;
&#xD;
          -  Insulin with or without oral agent treatment for diabetes mellitus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients using GLP1 (Glucagon-like peptide-1) agonists&#xD;
&#xD;
          -  Patients with eGFR&lt;30 (epidermal growth factor receptor) using (calculated CKD EPI)&#xD;
&#xD;
          -  Anemia (Hb&lt;11 grams)&#xD;
&#xD;
          -  Chronic liver chronic disease (ALT&gt;3xULN)&#xD;
&#xD;
          -  Use of glucocorticoids within 3 months preceding the investigation&#xD;
&#xD;
          -  Neoplasia treatment&#xD;
&#xD;
          -  Inability by the patient or caretaker to commit to protocol instructions and visit&#xD;
             schedule.&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Silmara Leite, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cline Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cline Research Center</name>
      <address>
        <city>Curitiba</city>
        <state>PR</state>
        <zip>80030480</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://doi.org/10.2337/dc17-1600</url>
    <description>International Consensus o use of Continuous Glucose Monitoring. Diabetes Care 2017;40:1631-1640</description>
  </link>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pubmed/30017799</url>
    <description>The physiology of endocrine systems with ageing</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/29417185</url>
    <description>Diabetes in the older patient: heterogeneity requires individualization of therapeutic strategies</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/28828487</url>
    <description>Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/15840177</url>
    <description>Estimating the mean and variance from the median, range, and the size of a sample.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/19565683</url>
    <description>A power primer.</description>
  </link>
  <link>
    <url>https://doi.org/10.2337/dci19-0028</url>
    <description>Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/30575414</url>
    <description>The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes.</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>May 6, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 12, 2022</last_update_submitted>
  <last_update_submitted_qc>June 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cline Research Center</investigator_affiliation>
    <investigator_full_name>Silmara Leite</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Type 2 Diabetes</keyword>
  <keyword>Elderly</keyword>
  <keyword>Continuous Glucose Monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT04411277
org study id: ADC-OUS-IIS-19-47
nct id: NCT04411277
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Prospective observational cohort study. Elderly patients >65 years with type 2 diabetes
      mellitus (T2DM) on insulin therapy and HbA1c between 7% and 9%, with or without oral agents,
      will be identified from medical records and invited to participate. Patients will wear a
      FreeStyle Libre Flash CGM during a 6-week study period.

      Using CGM technology, we will assess an efficacy outcome : time in range (TIR) between 70-180
      mg/dl and a safety outcome: incidence of hypoglycemia (time below range (TBR) less than 70,
      54, and 40 mg/dl in insulin treated older adults with T2DM.

      Patients will return to clinic every 2 weeks for new continuous glucose monitoring (CGM)
      placement, assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.

      CGM data will be downloaded every 2 weeks.
Prospective observational cohort study. Patients over 65 years of age, with TDM2 using
      insulin with or without the use of associated oral antidiabetic agents and with HbA1c between
      7% and 9%, will be identified by medical records at the Hospital da Cruz Vermelha
      Brasileira-Filial do Paraná and they will be invited to participate in the study by telephone
      and forwarded to the research center Cline Research Center where the study procedures will be
      carried out. Patients from the private clinic of neurology and endocrinology Cline will also
      be invited by telephone. In this way the sample of patients will include patients from the
      public and private health system.

      On the first visit to the research centers, after signing the informed consent form (ICF),
      patients will be evaluated for the presence of other comorbidities associated with diabetes
      such as the presence of cardiovascular disease, hypertension and dyslipidemia.

      The screening for the presence of sarcopenia will be performed with the application of the
      SARC-F questionnaire; measuring muscle strength with grip strength; the functional test of
      getting up from the chair without supporting the arms and walking for 3 meters, turning 180º
      and returning to sit. The time in which the elderly person performs this task is timed and
      the time up to 20 seconds is considered normal.

      Patients will undergo a complete physical examination and body composition analysis using the
      InBody 270 multifrequency bioimpedance to calculate the appendicular skeletal musculature.

      After the first evaluation at the research centers, patients will be referred to partner
      laboratories that use the same methodologies for measuring HbA1c, blood count, urea,
      creatinine, glutamic oxalacetic transaminase (TGO) and glutamic-pyruvic transaminase (TGP),
      which will be performed only at the initial visit.

      During the second visit to the research center, the FreeStyle Libre Flash interstitial
      glucose sensor will be inserted for the first time in the posterior and upper arm and the
      patient will be instructed to read the glucose at least 10 times a day, being sure to check
      glucose for a period longer than 8 hours. The patient should be instructed to return to the
      research center every 2 weeks to change the sensor until completing the 6-week period.

      The patient's travel to the research center will be reimbursed by the study team. The study
      will be carried out at the Hospital da Cruz Vermelha Brasileira-Filial do Paraná, located in
      Curitiba in partnership with the independent research center Cline Research Center (CRC).
      Eligible patients will be randomly selected from clinical outpatients at participating
      institutions, concomitantly.
observational model: Cohort
time perspective: Prospective
measure: Primary outcome is time in range (TIR)
time frame: 04-07-2021
description: TIR between 70-180 mg/dL in insulin treated in patients older than 65 years.
measure: -Frequency of hypoglycemia (<70mg/dL, <54mg/dL) to measure Time Bellow Range
time frame: 04-07-2021
description: percentage of patients with greater than 5%-time below glucose target (<70 mg/dL);
diurnal and nocturnal hypoglycemia;
measure: -Time in hyperglycemia > 180, 250 mg/dL to measure Time Above Range
time frame: 04-07-2021
description: percentage of patients with greater than 5%-time glucose above 250mg/dL
percentage of patients with greater than 25%-time glucose above 180mg/dL
measure: -Adherence to CGM use and sensor utilization for diabetes care management using CGM
time frame: 04-07-2021
description: -assessing the percentage of captured sensor data
measure: - Rate of emergency room visits and hospitalization
time frame: 04-07-2021
description: -changing insulin type and dose to prevent hospitalization
measure: -Glucose Variability
time frame: 04-07-2021
description: glycemic variability standard deviation and MAGE(mean amplitude of glycemic excursions)
glucose variability will be calculated as % coefficient of variation %CV= (standard deviation (SD)/mean glucose x 100%)
arm group label: T2DM Elderly on Insulin CGM
description: 70 patients with type 2 diabetes > 65 years of age taking insulin as treatment. The sample size was calculated to estimate the minimal number of patients necessary to describe the mean TIR (minutes/day).
intervention type: Device
intervention name: Application of the FreeStyle Libre Flash Glucose CGM.
description: Assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.
arm group label: T2DM Elderly on Insulin CGM
intervention type: Diagnostic Test
intervention name: InBody 270 multifrequency bioimpedance
description: analysis of body composition to calculate appendicular skeletal muscle.
arm group label: T2DM Elderly on Insulin CGM
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Silmara Leite, MD, PhD
role: Principal Investigator
affiliation: Cline Research Center
facility: 
country: Brazil
url: http://doi.org/10.2337/dc17-1600
description: International Consensus o use of Continuous Glucose Monitoring. Diabetes Care 2017;40:1631-1640
url: http://www.ncbi.nlm.nih.gov/pubmed/30017799
description: The physiology of endocrine systems with ageing
url: https://www.ncbi.nlm.nih.gov/pubmed/29417185
description: Diabetes in the older patient: heterogeneity requires individualization of therapeutic strategies
url: https://www.ncbi.nlm.nih.gov/pubmed/28828487
description: Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial.
url: https://www.ncbi.nlm.nih.gov/pubmed/15840177
description: Estimating the mean and variance from the median, range, and the size of a sample.
url: https://www.ncbi.nlm.nih.gov/pubmed/19565683
description: A power primer.
url: https://doi.org/10.2337/dci19-0028
description: Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range
url: https://www.ncbi.nlm.nih.gov/pubmed/30575414
description: The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes.
responsible party type: Principal Investigator
investigator affiliation: Cline Research Center
investigator full name: Silmara Leite
investigator title: Director
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No