<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/NCT03254849</url>
  </required_header>
  <id_info>
    <org_study_id>00/0764-Empa2</org_study_id>
    <nct_id>NCT03254849</nct_id>
  </id_info>
  <brief_title>Empagliflozin and Sympathetic Nerve Traffic</brief_title>
  <official_title>Effects on Blood Pressure and Central Sympathetic Nerve Traffic by SGLT2-inhibition With Empagliflozin Compared to Hydrochlorothiazide in Patients With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Profil Institut für Stoffwechselforschung GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Profil Institut für Stoffwechselforschung GmbH</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>
      In this study the effects of the Inhibition of the Sodium-Glucose Linked Transporter 2 in the&#xD;
      kidney with empagliflozin compared to hydrochlorothiazide on blood pressure and on central&#xD;
      sympathic nervous activity will be examined.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug empagliflozin is a selective oral inhibitor of the sodium-glucose co-transporter 2&#xD;
      (SGLT-2) in the kidney.On the market empagliflozin is approved for the treatment of type 2&#xD;
      Diabetes. The mechanism of action can be described as follows: SGLT-2 is responsible for 90%&#xD;
      of the reabsorption of Glucose in the kidney. If this Transport System is inhibited the&#xD;
      secretion of glucose via the urine is increased. Therefore the blood glucose concentration&#xD;
      will be lowered.&#xD;
&#xD;
      It has been noted that the SGLT-2 drugs are lowering the blood pressure as well, but the&#xD;
      specific characteristics of the durg leading to this effect have not been examined in&#xD;
      adequate clinical trial up to now.&#xD;
&#xD;
      To evaluate the central sympathic nervous activity a microneurography will be performed in&#xD;
      this study; this examination will provide Information if empagliflozin dose decrease the&#xD;
      sympathic nervous activity. If this is the case new effects of empagliflozin have to be&#xD;
      discussed, Otherwise it can be assumed that the blood pressure decrease is a result of an&#xD;
      increase of urine volume. In this case the sympathic activity should be increased.&#xD;
&#xD;
      This study will be performed in parallel groups who will receive a double-blind, randomised&#xD;
      treatment, either empagliflozin or hydrochlorothiazide. The hypothesis that empagliflozin -&#xD;
      in contrast to hydrochlorthiazide - does not increase the sympathic nervous activity in&#xD;
      obese, hypertensive subjects with type 2 Diabetes treated with metformin will be tested.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 8, 2017</start_date>
  <completion_date type="Actual">April 20, 2020</completion_date>
  <primary_completion_date type="Actual">April 20, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood Pressure reduction</measure>
    <time_frame>6 weeks</time_frame>
    <description>Blood pressure reduction with empagliflozin treatment is associated with lesser increase in sympathetic nerve traffic when compared to Hydrochlorothiazide treatment</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>empagliflozin 25 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will take 2 tablets each day to ensure double-blind Treatment. Arm 1: 25 mg/d empagliflozin + hydrochlorothiazide placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hydrochlorothiazide 25 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will take 2 tablets each day to ensure double-blind Treatment. Arm 2: 25 mg/d hydrochlorothiazide + empagliflozin placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Empagliflozin</intervention_name>
    <description>1 tablet</description>
    <arm_group_label>empagliflozin 25 mg</arm_group_label>
    <other_name>Jardiance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrochlorothiazide 25 mg</intervention_name>
    <description>1 tablet</description>
    <arm_group_label>hydrochlorothiazide 25 mg</arm_group_label>
    <other_name>HCT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women and men &gt;= 50 and &lt;= 80 years of age&#xD;
&#xD;
          -  type 2 diabetes mellitus for &gt;=2 years&#xD;
&#xD;
          -  only metformin monotherapy is allowed; metformin dose must have been stable for &gt;=12&#xD;
             weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous empagliflozin treatment within the last 3 months&#xD;
&#xD;
          -  heart failure NYHA II - IV&#xD;
&#xD;
          -  subjects who have received any investigational medicinal product or have used any&#xD;
             investigational medical device within 30 days prior to the screening visit, or who are&#xD;
             actively participating in any investigational medicinal product or medical device&#xD;
             trial, or who are scheduled for any such trial during the course of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim Heise, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Profil Institut für Stoffwechselforschung GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Profil Institut für Stoffwechselforschung GmbH</name>
      <address>
        <city>Neuss</city>
        <state>North Rhine-Westphalia</state>
        <zip>41460</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>July 13, 2020</last_update_submitted>
  <last_update_submitted_qc>July 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</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>Diabetes Mellitus</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>Empagliflozin</mesh_term>
    <mesh_term>Hydrochlorothiazide</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/NCT03254849
org study id: 00/0764-Empa2
nct id: NCT03254849
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In this study the effects of the Inhibition of the Sodium-Glucose Linked Transporter 2 in the
      kidney with empagliflozin compared to hydrochlorothiazide on blood pressure and on central
      sympathic nervous activity will be examined.
The drug empagliflozin is a selective oral inhibitor of the sodium-glucose co-transporter 2
      (SGLT-2) in the kidney.On the market empagliflozin is approved for the treatment of type 2
      Diabetes. The mechanism of action can be described as follows: SGLT-2 is responsible for 90%
      of the reabsorption of Glucose in the kidney. If this Transport System is inhibited the
      secretion of glucose via the urine is increased. Therefore the blood glucose concentration
      will be lowered.

      It has been noted that the SGLT-2 drugs are lowering the blood pressure as well, but the
      specific characteristics of the durg leading to this effect have not been examined in
      adequate clinical trial up to now.

      To evaluate the central sympathic nervous activity a microneurography will be performed in
      this study; this examination will provide Information if empagliflozin dose decrease the
      sympathic nervous activity. If this is the case new effects of empagliflozin have to be
      discussed, Otherwise it can be assumed that the blood pressure decrease is a result of an
      increase of urine volume. In this case the sympathic activity should be increased.

      This study will be performed in parallel groups who will receive a double-blind, randomised
      treatment, either empagliflozin or hydrochlorothiazide. The hypothesis that empagliflozin -
      in contrast to hydrochlorthiazide - does not increase the sympathic nervous activity in
      obese, hypertensive subjects with type 2 Diabetes treated with metformin will be tested.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Blood Pressure reduction
time frame: 6 weeks
description: Blood pressure reduction with empagliflozin treatment is associated with lesser increase in sympathetic nerve traffic when compared to Hydrochlorothiazide treatment
arm group label: empagliflozin 25 mg
arm group type: Experimental
description: Each patient will take 2 tablets each day to ensure double-blind Treatment. Arm 1: 25 mg/d empagliflozin + hydrochlorothiazide placebo
arm group label: hydrochlorothiazide 25 mg
arm group type: Experimental
description: Each patient will take 2 tablets each day to ensure double-blind Treatment. Arm 2: 25 mg/d hydrochlorothiazide + empagliflozin placebo
intervention type: Drug
intervention name: Empagliflozin
description: 1 tablet
arm group label: empagliflozin 25 mg
other name: Jardiance
intervention type: Drug
intervention name: Hydrochlorothiazide 25 mg
description: 1 tablet
arm group label: hydrochlorothiazide 25 mg
other name: HCT
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Tim Heise, MD
role: Principal Investigator
affiliation: Profil Institut für Stoffwechselforschung GmbH
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Empagliflozin
mesh term: Hydrochlorothiazide