<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/NCT03014011</url>
  </required_header>
  <id_info>
    <org_study_id>MISP</org_study_id>
    <nct_id>NCT03014011</nct_id>
  </id_info>
  <brief_title>Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes</brief_title>
  <official_title>Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Gentofte, Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Psychiatric Centre Rigshospitalet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bispebjerg Hospital</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>
      Hypoglycaemia in subjects suffering from type 2 diabetes may have substantial consequences&#xD;
      including a significant negative impact on quality of life. Further, repeated minor&#xD;
      hypoglycaemias may result in significant productivity losses.&#xD;
&#xD;
      Here, the investigators propose to provide quantitative results on cognition during an acute&#xD;
      mild hypoglycaemic episode (target plasma glucose 3 mmol/L) in 28 subjects with type 2&#xD;
      diabetes. Data will be provided on executive function, attention and memory.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypoglycaemia in subjects suffering from type 2 diabetes may have substantial consequences&#xD;
      including a significant negative impact on quality of life. Further, repeated minor&#xD;
      hypoglycaemias may result in significant productivity losses. In healthy subjects a number of&#xD;
      studies show that during a hypoglycaemic episode with plasma levels of 2.2 - 2.5 mmol/L&#xD;
      (40-45 mg/dl) brain areas responsible for cognition have an altered neuronal function when&#xD;
      measuring cerebral blood flow. This is accompanied by severely impaired cognitive function&#xD;
      with a reduced ability to solve simple cognitive tasks. At higher levels of glucose (above 3&#xD;
      mmol/L (54 mg/dl)), it remains to be settled whether cognitive functions are also affected&#xD;
      negatively and whether this may be accompanied by changes in brain metabolism. Apart from&#xD;
      raising the blood glucose directly or indirectly via glucagon, no treatment for hypoglycaemia&#xD;
      exists, but since Glucagon-like peptide-1 (GLP-1) based therapies used in type 2 diabetes may&#xD;
      affect brain glucose consumption, therapeutic interventions to prevent negative results of&#xD;
      hypoglycaemia may eventually become clinically possible.&#xD;
&#xD;
      Here, the investigators propose to provide quantitative results on cognition during an acute&#xD;
      mild hypoglycaemic episode (target plasma glucose 3 mmol/L). Data will be provided on&#xD;
      executive function, attention and memory.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 13, 2017</start_date>
  <completion_date type="Actual">July 24, 2018</completion_date>
  <primary_completion_date type="Actual">July 23, 2018</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Psychomotor Speed</measure>
    <time_frame>All neurocognitive testing was assessed at each intervention when glucose levels had been stabile for 40 minutes, an average of 2 hours after clamp procedure start. The duration of neurocognitive testing was approximately 40 min.</time_frame>
    <description>Symbol Digit Modalities Test was used as a measurement of psychomotor speed.&#xD;
For the Symbol Digit Modalities Test, participants were required to use a coded key to match nine abstract symbols paired with numerical digits. The final score is the correct number of substitutions in 120 s, and scores range between 0 and 110. Higher values represent a better outcome.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Diabetes Mellitus, Type II</condition>
  <condition>Hypoglycemia</condition>
  <condition>Cognitive Change</condition>
  <arm_group>
    <arm_group_label>Hypoglycaemic clamp first, then euglyceamic clamp</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>First intervention with a hypoglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with an euglycaemic clamp (approximately 5 hours).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Euglycaemic clamp first, then hypoglycaemic clamp</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>First intervention with an euglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with a hypoglycaemic clamp (approximately 5 hours).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypoglycaemic clamp</intervention_name>
    <description>The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to lower and keep plasma blood glucose levels at 3 mmol/L for outcome measurements.</description>
    <arm_group_label>Euglycaemic clamp first, then hypoglycaemic clamp</arm_group_label>
    <arm_group_label>Hypoglycaemic clamp first, then euglyceamic clamp</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Euglycaemic clamp</intervention_name>
    <description>The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to keep plasma blood glucose levels at 6 mmol/L for outcome measurements.</description>
    <arm_group_label>Euglycaemic clamp first, then hypoglycaemic clamp</arm_group_label>
    <arm_group_label>Hypoglycaemic clamp first, then euglyceamic clamp</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed and written consent&#xD;
&#xD;
          -  Clinically diagnosed type 2 diabetes mellitus for at least 3 months (diagnosed&#xD;
             according to the criteria of the World Health Organization (WHO)).&#xD;
&#xD;
          -  Normal haemoglobin ≥ 8.0 mmol/L (male) or ≥ 6.4 mmol/L (female)&#xD;
&#xD;
          -  Male or female participants aged 35-70 years, both inclusive.&#xD;
&#xD;
          -  Treated with diet or any antidiabetic medication except sulfonylureas, meglitinides or&#xD;
             insulin.&#xD;
&#xD;
          -  HbA1c ≤ 9.0 % by local laboratory analysis.&#xD;
&#xD;
          -  BMI &gt;23 kg/m2 and &lt;35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receipt of any investigational medicinal product within 3 months before screening in&#xD;
             this trial.&#xD;
&#xD;
          -  Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase&#xD;
             (ASAT) &gt;2 times normal values) or history of hepatobiliary disorder.&#xD;
&#xD;
          -  Nephropathy (serum creatinine levels ≥ 126 μmol/L (male) or ≥ 111 μmol/L (female)).&#xD;
&#xD;
          -  Cardiac problems defined as decompensated heart failure (New York Heart Association&#xD;
             (NYHA) class III and IV) at any time and/or angina pectoris within the last 12 months&#xD;
             and/or acute myocardial infarction at any time.&#xD;
&#xD;
          -  Active or recent malignant disease.&#xD;
&#xD;
          -  Treatment with drugs that cannot be paused for 12 hours.&#xD;
&#xD;
          -  Repeated resting blood pressure at screening outside the range 90-140 mmHg for&#xD;
             systolic or 50-90 mmHg for diastolic. This exclusion criterion also pertains to&#xD;
             subjects taking antihypertensives.&#xD;
&#xD;
          -  Visual impairment or auditory impairment.&#xD;
&#xD;
          -  Known abnormalities of the central nervous system or any endocrinological (with the&#xD;
             exception of diabetes mellitus and euthyroid goiter), haematological, neurological,&#xD;
             psychiatric diseases or other major disorders that in the opinion of the investigator&#xD;
             precludes compliance with the protocol, evaluation of the results or represent an&#xD;
             unacceptable risk for the participant's safety.&#xD;
&#xD;
          -  Proliferative retinopathy (funduscopy performed within 3 months before the screening&#xD;
             is acceptable) and/or severe neuropathy.&#xD;
&#xD;
          -  Current treatment with systemic drugs, which may interfere with glucose metabolism.&#xD;
&#xD;
          -  Significant history of alcoholism or drug/chemical abuse as per investigator's&#xD;
             judgement.&#xD;
&#xD;
          -  Current tobacco user (smoking or nicotinic product use 3 months prior to screening).&#xD;
&#xD;
          -  Severe hypoglycaemic event during the past 6 months.&#xD;
&#xD;
          -  Known hypoglycaemia unawareness.&#xD;
&#xD;
          -  Participants with mental incapacity or language barriers precluding adequate&#xD;
             understanding or co-operation or who, in the opinion of the investigator or their&#xD;
             general practitioner, should not participate in the trial.&#xD;
&#xD;
          -  For females only: Pregnancy, breast-feeding status or intention of becoming pregnant&#xD;
             during the trial.&#xD;
&#xD;
          -  Any chronic disorder or severe disease that in the opinion of the investigator might&#xD;
             endanger participant's safety or compliance with the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jørgen Rungby, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Endocrinology, Bispebjerg University Hospital, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Research in Endocrinology, Bispebjerg University Hospital</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <results_first_submitted>August 19, 2019</results_first_submitted>
  <results_first_submitted_qc>January 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 28, 2020</results_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bispebjerg Hospital</investigator_affiliation>
    <investigator_full_name>Malin Nilsson</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemic Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 15, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03014011/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>37 participants were screened between May 2017 and July 2018 at the Department of Endocrinology, Bispebjerg University Hospital, Denmark.</recruitment_details>
      <pre_assignment_details>Of the 37 screened participants, 28 met inclusion criteria and were randomised. 25 completed both intervention visits. Three participants (one man, two women) withdrew from the study after randomisation for reasons not related to the intervention. Baseline characteristics are based on the 25 participants that completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Hypoglycaemic Clamp Followed by Euglycaemic Clamp</title>
          <description>Participants completed a hypoglycaemic clamp on a first intervention visit. After a washout period of at least 2 weeks (maximum of 6 weeks), a euglycaemic clamp was performed on the second intervention visit.</description>
        </group>
        <group group_id="P2">
          <title>Euglycaemic Clamp Followed by Hypoglycaemic Clamp</title>
          <description>Participants completed a euglycaemic clamp on a first intervention visit. After a washout periodof at least 2 weeks (maximum of 6 weeks), a hypoglycaemic clamp was performed on the second intervention visit.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Randomised, double-blinded, crossover study design</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.2" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Psychomotor Speed</title>
        <description>Symbol Digit Modalities Test was used as a measurement of psychomotor speed.&#xD;
For the Symbol Digit Modalities Test, participants were required to use a coded key to match nine abstract symbols paired with numerical digits. The final score is the correct number of substitutions in 120 s, and scores range between 0 and 110. Higher values represent a better outcome.</description>
        <time_frame>All neurocognitive testing was assessed at each intervention when glucose levels had been stabile for 40 minutes, an average of 2 hours after clamp procedure start. The duration of neurocognitive testing was approximately 40 min.</time_frame>
        <population>The two interventions were hypoglycaemia (aiming for a plasma glucose target of 3.0 ± 0.2 mmol/l) and euglycaemia (plasma glucose clamp target 6.0 ± 0.2 mmol/l).</population>
        <group_list>
          <group group_id="O1">
            <title>Hypoglycaemia</title>
            <description>low glucose level</description>
          </group>
          <group group_id="O2">
            <title>Euglycaemia</title>
            <description>normal glucose level</description>
          </group>
        </group_list>
        <measure>
          <title>Psychomotor Speed</title>
          <description>Symbol Digit Modalities Test was used as a measurement of psychomotor speed.&#xD;
For the Symbol Digit Modalities Test, participants were required to use a coded key to match nine abstract symbols paired with numerical digits. The final score is the correct number of substitutions in 120 s, and scores range between 0 and 110. Higher values represent a better outcome.</description>
          <population>The two interventions were hypoglycaemia (aiming for a plasma glucose target of 3.0 ± 0.2 mmol/l) and euglycaemia (plasma glucose clamp target 6.0 ± 0.2 mmol/l).</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.7" spread="9.8"/>
                    <measurement group_id="O2" value="56.6" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>For each participant, adverse event data was collected from the day they were included, until the day after their second (and final) intervention visit, an average of 2 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Hypoglycaemic Clamp</title>
          <description>Mean plasma glucose concentration during the neurocognitive testing was 3.13 mmol/l for the hypoglycaemic clamp.</description>
        </group>
        <group group_id="E2">
          <title>Euglycaemic Clamp</title>
          <description>Mean plasma glucose concentration during the neurocognitive testing was 5.83 mmol/l for the euglycaemic clamp.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>MD Malin Nilsson</name_or_title>
      <organization>Bispebjerg Hospital</organization>
      <phone>50595861 ext 0045</phone>
      <email>mnil0028@regionh.dk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03014011
org study id: MISP
nct id: NCT03014011
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Hypoglycaemia in subjects suffering from type 2 diabetes may have substantial consequences
      including a significant negative impact on quality of life. Further, repeated minor
      hypoglycaemias may result in significant productivity losses.

      Here, the investigators propose to provide quantitative results on cognition during an acute
      mild hypoglycaemic episode (target plasma glucose 3 mmol/L) in 28 subjects with type 2
      diabetes. Data will be provided on executive function, attention and memory.
Hypoglycaemia in subjects suffering from type 2 diabetes may have substantial consequences
      including a significant negative impact on quality of life. Further, repeated minor
      hypoglycaemias may result in significant productivity losses. In healthy subjects a number of
      studies show that during a hypoglycaemic episode with plasma levels of 2.2 - 2.5 mmol/L
      (40-45 mg/dl) brain areas responsible for cognition have an altered neuronal function when
      measuring cerebral blood flow. This is accompanied by severely impaired cognitive function
      with a reduced ability to solve simple cognitive tasks. At higher levels of glucose (above 3
      mmol/L (54 mg/dl)), it remains to be settled whether cognitive functions are also affected
      negatively and whether this may be accompanied by changes in brain metabolism. Apart from
      raising the blood glucose directly or indirectly via glucagon, no treatment for hypoglycaemia
      exists, but since Glucagon-like peptide-1 (GLP-1) based therapies used in type 2 diabetes may
      affect brain glucose consumption, therapeutic interventions to prevent negative results of
      hypoglycaemia may eventually become clinically possible.

      Here, the investigators propose to provide quantitative results on cognition during an acute
      mild hypoglycaemic episode (target plasma glucose 3 mmol/L). Data will be provided on
      executive function, attention and memory.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
measure: Psychomotor Speed
time frame: All neurocognitive testing was assessed at each intervention when glucose levels had been stabile for 40 minutes, an average of 2 hours after clamp procedure start. The duration of neurocognitive testing was approximately 40 min.
description: Symbol Digit Modalities Test was used as a measurement of psychomotor speed.
For the Symbol Digit Modalities Test, participants were required to use a coded key to match nine abstract symbols paired with numerical digits. The final score is the correct number of substitutions in 120 s, and scores range between 0 and 110. Higher values represent a better outcome.
arm group label: Hypoglycaemic clamp first, then euglyceamic clamp
arm group type: Other
description: First intervention with a hypoglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with an euglycaemic clamp (approximately 5 hours).
arm group label: Euglycaemic clamp first, then hypoglycaemic clamp
arm group type: Other
description: First intervention with an euglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with a hypoglycaemic clamp (approximately 5 hours).
intervention type: Other
intervention name: Hypoglycaemic clamp
description: The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to lower and keep plasma blood glucose levels at 3 mmol/L for outcome measurements.
arm group label: Euglycaemic clamp first, then hypoglycaemic clamp
arm group label: Hypoglycaemic clamp first, then euglyceamic clamp
intervention type: Other
intervention name: Euglycaemic clamp
description: The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to keep plasma blood glucose levels at 6 mmol/L for outcome measurements.
arm group label: Euglycaemic clamp first, then hypoglycaemic clamp
arm group label: Hypoglycaemic clamp first, then euglyceamic clamp
criteria: 
gender: All
minimum age: 35 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jørgen Rungby, Professor
role: Principal Investigator
affiliation: Department of Endocrinology, Bispebjerg University Hospital, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Bispebjerg Hospital
investigator full name: Malin Nilsson
investigator title: MD
mesh term: Diabetes Mellitus
mesh term: Hypoglycemia
mesh term: Diabetes Mellitus, Type 2
mesh term: Hypoglycemic Agents
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 