<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/NCT02991365</url>
  </required_header>
  <id_info>
    <org_study_id>8 weeks study</org_study_id>
    <nct_id>NCT02991365</nct_id>
  </id_info>
  <brief_title>Effect of Weight Loss on Brain Insulin Sensitivity in Humans</brief_title>
  <official_title>Effekt Von Gewichtsabnahme Auf Die zentralnervöse Insulinresistenz Des Menschen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Tuebingen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obesity if known to be associated with brain insulin resistance in humans. This condition has&#xD;
      not only implication for the brain but also for whole-body energy homeostasis. Research in&#xD;
      rodents indicates that weight loss is able to improve insulin sensitivity of the brain. The&#xD;
      current project will test this hypothesis in humans. Therefore, brain insulin sensitivity&#xD;
      will be assessed by fMRI in combination with intranasal insulin administration, using an&#xD;
      established protocol. Furthermore, effects of daily administration of insulin nasal spray&#xD;
      (versus placebo) over 8 weeks will be assessed as secondary (exploratory) variables.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>brain insulin sensitivity</measure>
    <time_frame>30 minutes after administration of nasal insulin</time_frame>
    <description>fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight.</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance .</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition .</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>whole-body insulin sensitivity</measure>
    <time_frame>2 hours</time_frame>
    <description>Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose tolerance</measure>
    <time_frame>2 hours</time_frame>
    <description>a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>1 hours</time_frame>
    <description>cognitive function will be addressed by neuropsychological testing.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>nasal insulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>daily administration of 160 U of human insulin as nasal spray</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo spray</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>daily administration of placebo solution as nasal spray</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>nasal insulin</intervention_name>
    <arm_group_label>nasal insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo spray</intervention_name>
    <arm_group_label>placebo spray</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HbA1c &lt;6.5%&#xD;
&#xD;
          -  Age between 40 and 75 years&#xD;
&#xD;
          -  No intake of antidiabetic drugs or drugs for weight reduction&#xD;
&#xD;
          -  no steroid intake&#xD;
&#xD;
          -  Stable medication over 10 weeks before the start of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Persons who wear non-removable metal parts in or on the body.&#xD;
&#xD;
          -  Persons with reduced temperature sensitivity and / or increased sensitivity to heating&#xD;
             of the body&#xD;
&#xD;
          -  Cardiovascular disease can not be ruled out, e.g. manifest coronary heart disease,&#xD;
             heart failure greater than NYHA 2, previous heart attack, stroke condition&#xD;
&#xD;
          -  Persons with hearing impairment or increased sensitivity to loud noises&#xD;
&#xD;
          -  People with claustrophobia&#xD;
&#xD;
          -  Minors or non-consenting subjects are also excluded&#xD;
&#xD;
          -  Subjects with an operation less than 3 months&#xD;
&#xD;
          -  Simultaneous participation in other studies&#xD;
&#xD;
          -  Neurological and psychiatric disorders&#xD;
&#xD;
          -  Subjects with hemoglobin Hb &lt;11 g / dl&#xD;
&#xD;
          -  Hypersensitivity to any of the substances used&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreas Fritsche, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Tübingen Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andreas Fritsche, MD</last_name>
    <phone>+49 7071 29 80687</phone>
    <email>andreas.fritsche@med.uni-tuebingen.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Tuebingen, Department of Internal Medicine IV</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Fritsche, Prof. Dr.</last_name>
      <phone>+49 7071 29 82714</phone>
      <email>andreas.fritsche@med.uni-tuebingen.de</email>
    </contact>
    <contact_backup>
      <last_name>Martin Heni, Dr.</last_name>
      <phone>+49 7071 29 82714</phone>
      <email>martin.heni@med.uni-tuebingen.de</email>
    </contact_backup>
    <investigator>
      <last_name>Martin Heni, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>March 25, 2022</last_update_submitted>
  <last_update_submitted_qc>March 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2022</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>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_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/NCT02991365
org study id: 8 weeks study
nct id: NCT02991365
lead sponsor: 
has dmc: No
Obesity if known to be associated with brain insulin resistance in humans. This condition has
      not only implication for the brain but also for whole-body energy homeostasis. Research in
      rodents indicates that weight loss is able to improve insulin sensitivity of the brain. The
      current project will test this hypothesis in humans. Therefore, brain insulin sensitivity
      will be assessed by fMRI in combination with intranasal insulin administration, using an
      established protocol. Furthermore, effects of daily administration of insulin nasal spray
      (versus placebo) over 8 weeks will be assessed as secondary (exploratory) variables.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: brain insulin sensitivity
time frame: 30 minutes after administration of nasal insulin
description: fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.
measure: Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight.
time frame: 8 weeks
description: Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded.
measure: Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance .
time frame: 8 weeks
description: Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test.
measure: Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition .
time frame: 8 weeks
description: Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS.
measure: whole-body insulin sensitivity
time frame: 2 hours
description: Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.
measure: Glucose tolerance
time frame: 2 hours
description: a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria.
measure: Cognitive function
time frame: 1 hours
description: cognitive function will be addressed by neuropsychological testing.
arm group label: nasal insulin
arm group type: Active Comparator
description: daily administration of 160 U of human insulin as nasal spray
arm group label: placebo spray
arm group type: Placebo Comparator
description: daily administration of placebo solution as nasal spray
intervention type: Other
intervention name: nasal insulin
arm group label: nasal insulin
intervention type: Other
intervention name: placebo spray
arm group label: placebo spray
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andreas Fritsche, MD
role: Principal Investigator
affiliation: University of Tübingen Hospital
last name: Andreas Fritsche, MD
phone: +49 7071 29 80687
email: andreas.fritsche@med.uni-tuebingen.de
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Germany
responsible party type: Sponsor
mesh term: Insulin Resistance
mesh term: Insulin
sharing ipd: No