<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/NCT02192450</url>
  </required_header>
  <id_info>
    <org_study_id>HypoDeg</org_study_id>
    <nct_id>NCT02192450</nct_id>
  </id_info>
  <brief_title>Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia</brief_title>
  <acronym>HypoDeg</acronym>
  <official_title>The Effect of Insulin Degludec on Risk of Symptomatic Nocturnal Hypoglycaemia in Subjects With Type 1 Diabetes and High Risk of Nocturnal Severe Hypoglycaemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordsjaellands Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Steno Diabetes Center Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Copenhagen University Hospital, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital of South West Jutland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nordsjaellands Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether insulin degludec compared to insulin&#xD;
      glargine can reduce the risk of symptomatic nocturnal hypoglycaemia in subjects with the&#xD;
      greatest potential benefit from optimised insulin treatment, which are patients with type 1&#xD;
      diabetes and high risk of nocturnal severe hypoglycaemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Insulin degludec is a novel insulin analogue that may reduce the risk of mild&#xD;
      nocturnal hypoglycaemia in type 1 diabetes. Patients with type 1 diabetes and recurrent&#xD;
      severe hypoglycaemia (high risk patients) are also burdened by nocturnal hyoglycaemia (mild&#xD;
      and silent). These episodes may contribute to the developement of hormonal counterregulatory&#xD;
      failure and hypoglycaemia unawareness, which in turn increases the risk of further&#xD;
      hypoglycaemic episodes, especially epiosdes of severe hypoglycaemia.The effect of insulin&#xD;
      degludec on risk of mild nocturnal hypoglycaemia in subjects with type 1 diabetes and high&#xD;
      risk of severe hypoglycaemia compared to insulin glargine is to be investigated.&#xD;
&#xD;
      Study design and intervention: A controlled, cross-over multi-centre study in a Prospective,&#xD;
      Randomised, Open, Blinded Endpoint (PROBE) design. Each treatment period last for 12 months.&#xD;
      Patients will be randomised to treatment with basal-bolus therapy with insulin&#xD;
      aspart/degludec or insulin aspart/glargine in random order. Endpoints will be assessed during&#xD;
      the last 9 months of each treatment arm.&#xD;
&#xD;
      Subjects: 175 type 1 diabetic patients with a history of one or more episodes of nocturnal&#xD;
      severe hypoglycaemia during the proceeding two years.&#xD;
&#xD;
      Method: Patients will record all events of symptomatic (mild), asymptomatic (silent) and&#xD;
      severe hypoglycaemia in a diary. All events of symptomatic nocturnal and severe hypoglycaemia&#xD;
      must also be reported by telephone within 24 hours. Patients will be instructed to do and&#xD;
      record self-monitored blood glucose (SMBG) i.e. 4-point profiles twice per week (blood&#xD;
      glucose before breakfast, before lunch, before dinner and before bedtime).&#xD;
&#xD;
      Outcomes: See &quot;Outcome Measures&quot;. Concerning the primary endpoint all possible symptomatic&#xD;
      nocturnal hypoglycaemic episodes will be adjudicated by an independent endpoint committee&#xD;
      consisting of diabetes specialists blinded to the individual patient insulin regimen.&#xD;
&#xD;
      Safety: Adverse reactions&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">February 28, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Symptomatic nocturnal hypoglycaemia</measure>
    <time_frame>9 months (3-12) of each treatment period</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severe hypoglycaemia (total, night-time, daytime)</measure>
    <time_frame>9 months (3-12) of each treatment period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any nocturnal hypoglycaemia (incl. asymptomatic/silent events)</measure>
    <time_frame>9 months (3-12) of each treatment period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any daytime hypoglycaemia (symptomatic, asymptomatic/silent and severe)</measure>
    <time_frame>9 months (3-12) of each treatment period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any CGM recorded hypoglycaemia (symptomatic, asymptomatic/silent and severe)</measure>
    <time_frame>2 x 6 days in each treatment arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any in-hospital nocturnal hypoglycaemia (incl. asymptomatic/silent events)</measure>
    <time_frame>2 overnight stays in each treatment arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>From baseline to after 12 months of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glycaemic variability</measure>
    <time_frame>4 x overnight stays and 4 x 6 days of CGM</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin doses</measure>
    <time_frame>End of each treatment period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life incl. pre-depression scale</measure>
    <time_frame>At baseline, cross-over and after 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">149</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <condition>Nocturnal Hypoglycemia</condition>
  <condition>Recurrent Severe Hypoglycaemia</condition>
  <arm_group>
    <arm_group_label>Insulin glargine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.&#xD;
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.&#xD;
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.&#xD;
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin degludec</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.&#xD;
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.&#xD;
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.&#xD;
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin aspart/glargine</intervention_name>
    <arm_group_label>Insulin glargine</arm_group_label>
    <other_name>NovoRapid</other_name>
    <other_name>Lantus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin aspart/degludec</intervention_name>
    <arm_group_label>Insulin degludec</arm_group_label>
    <other_name>NovoRapid</other_name>
    <other_name>Tresiba</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes &gt; 5 years&#xD;
&#xD;
          -  One or more episodes of nocturnal severe hypoglycaemia during the preceding two years&#xD;
&#xD;
          -  Treated with multiple dose insulin injection (&gt;2) or insulin pump. Both human insulin&#xD;
             and insulin analogues are allowed&#xD;
&#xD;
          -  Willingness to a once daily (OD) regimen concerning insulin degludec and insulin&#xD;
             glargine&#xD;
&#xD;
          -  Willingness to do self-monitoring of blood glucose (SMBG) and keep a diary&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of primary and secondary adrenal insufficiency, growth hormone deficiency, or&#xD;
             untreated myxoedema&#xD;
&#xD;
          -  History of unstable angina or major cardiovascular events (myocardial infarction,&#xD;
             coronary re-vascularisation, transient ischaemic attack, or stroke within the last&#xD;
             three months)&#xD;
&#xD;
          -  Heart failure, New York Heart Association (NYHA) class IV&#xD;
&#xD;
          -  History of malignancy unless a disease-free period exceeding five years&#xD;
&#xD;
          -  History of alcohol or drug abuse&#xD;
&#xD;
          -  Treatment with glucose lowering agent(s) other than insulin&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Women of childbearing potential who are not using chemical (P-pills or gestagen&#xD;
             depots) or mechanical (intra-uterine device) contraception&#xD;
&#xD;
          -  Participation in another investigational drug study within the last 3 months&#xD;
&#xD;
          -  Inability to understand the informed consent&#xD;
&#xD;
          -  HbA1c &gt; 86 mmol/mol (10%)&#xD;
&#xD;
          -  Shifting working hours&#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>Ulrik Pedersen-Bjergaard, MD, DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nordsjaellands Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nordsjaellands Hospital</name>
      <address>
        <city>Hilleroed</city>
        <zip>3400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>June 26, 2019</last_update_submitted>
  <last_update_submitted_qc>June 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>Hypoglycaemia</keyword>
  <keyword>Glucose Metabolism Disorders</keyword>
  <keyword>Metabolic Diseases</keyword>
  <keyword>Endocrine System Diseases</keyword>
  <keyword>Autoimmune Diseases</keyword>
  <keyword>Insulin</keyword>
  <keyword>Hypoglycaemic Agents</keyword>
  <keyword>Physiological Effetcs of Drugs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Insulin Aspart</mesh_term>
    <mesh_term>Insulin, Long-Acting</mesh_term>
    <mesh_term>Insulin degludec, insulin aspart drug combination</mesh_term>
  </intervention_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/NCT02192450
org study id: HypoDeg
nct id: NCT02192450
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether insulin degludec compared to insulin
      glargine can reduce the risk of symptomatic nocturnal hypoglycaemia in subjects with the
      greatest potential benefit from optimised insulin treatment, which are patients with type 1
      diabetes and high risk of nocturnal severe hypoglycaemia.
Background: Insulin degludec is a novel insulin analogue that may reduce the risk of mild
      nocturnal hypoglycaemia in type 1 diabetes. Patients with type 1 diabetes and recurrent
      severe hypoglycaemia (high risk patients) are also burdened by nocturnal hyoglycaemia (mild
      and silent). These episodes may contribute to the developement of hormonal counterregulatory
      failure and hypoglycaemia unawareness, which in turn increases the risk of further
      hypoglycaemic episodes, especially epiosdes of severe hypoglycaemia.The effect of insulin
      degludec on risk of mild nocturnal hypoglycaemia in subjects with type 1 diabetes and high
      risk of severe hypoglycaemia compared to insulin glargine is to be investigated.

      Study design and intervention: A controlled, cross-over multi-centre study in a Prospective,
      Randomised, Open, Blinded Endpoint (PROBE) design. Each treatment period last for 12 months.
      Patients will be randomised to treatment with basal-bolus therapy with insulin
      aspart/degludec or insulin aspart/glargine in random order. Endpoints will be assessed during
      the last 9 months of each treatment arm.

      Subjects: 175 type 1 diabetic patients with a history of one or more episodes of nocturnal
      severe hypoglycaemia during the proceeding two years.

      Method: Patients will record all events of symptomatic (mild), asymptomatic (silent) and
      severe hypoglycaemia in a diary. All events of symptomatic nocturnal and severe hypoglycaemia
      must also be reported by telephone within 24 hours. Patients will be instructed to do and
      record self-monitored blood glucose (SMBG) i.e. 4-point profiles twice per week (blood
      glucose before breakfast, before lunch, before dinner and before bedtime).

      Outcomes: See "Outcome Measures". Concerning the primary endpoint all possible symptomatic
      nocturnal hypoglycaemic episodes will be adjudicated by an independent endpoint committee
      consisting of diabetes specialists blinded to the individual patient insulin regimen.

      Safety: Adverse reactions
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Symptomatic nocturnal hypoglycaemia
time frame: 9 months (3-12) of each treatment period
measure: Severe hypoglycaemia (total, night-time, daytime)
time frame: 9 months (3-12) of each treatment period
measure: Any nocturnal hypoglycaemia (incl. asymptomatic/silent events)
time frame: 9 months (3-12) of each treatment period
measure: Any daytime hypoglycaemia (symptomatic, asymptomatic/silent and severe)
time frame: 9 months (3-12) of each treatment period
measure: Any CGM recorded hypoglycaemia (symptomatic, asymptomatic/silent and severe)
time frame: 2 x 6 days in each treatment arm
measure: Any in-hospital nocturnal hypoglycaemia (incl. asymptomatic/silent events)
time frame: 2 overnight stays in each treatment arm
measure: Change in HbA1c
time frame: From baseline to after 12 months of treatment
measure: Change in glycaemic variability
time frame: 4 x overnight stays and 4 x 6 days of CGM
measure: Insulin doses
time frame: End of each treatment period
measure: Quality of life incl. pre-depression scale
time frame: At baseline, cross-over and after 24 months
arm group label: Insulin glargine
arm group type: Active Comparator
description: Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals.
arm group label: Insulin degludec
arm group type: Experimental
description: Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals.
intervention type: Drug
intervention name: Insulin aspart/glargine
arm group label: Insulin glargine
other name: NovoRapid
other name: Lantus
intervention type: Drug
intervention name: Insulin aspart/degludec
arm group label: Insulin degludec
other name: NovoRapid
other name: Tresiba
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ulrik Pedersen-Bjergaard, MD, DMSc
role: Principal Investigator
affiliation: Nordsjaellands Hospital
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemia
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Aspart
mesh term: Insulin, Long-Acting
mesh term: Insulin degludec, insulin aspart drug combination