<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/NCT04420650</url>
  </required_header>
  <id_info>
    <org_study_id>BRAINSTIM</org_study_id>
    <nct_id>NCT04420650</nct_id>
  </id_info>
  <brief_title>Improving Insulin Sensitivity by Non-invasive Brain Stimulation</brief_title>
  <official_title>Improving Insulin Sensitivity by Non-invasive Brain Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Center for Diabetes Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Tuebingen</source>
  <oversight_info>
    <has_dmc>No</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>
      Efforts in curing and preventing obesity and type 2 diabetes (T2D) have been elusive thus&#xD;
      far. One reason for that is the lack of understanding of the role of the brain in the&#xD;
      development and treatment of the disease. In recent studies, the hypothalamus was identified&#xD;
      as part of a brain network including higher cognitive regions that is particularly vulnerable&#xD;
      to insulin resistance. Furthermore, the central insulin response in this network predicted&#xD;
      food craving and hunger. In this project, transcranial direct current stimulation (tDCS) is&#xD;
      implemented as a tool to stimulate brain networks. The investigators hypothesize that&#xD;
      stimulating the hypothalamus-cognitive network will enhance insulin sensitivity and reduce&#xD;
      food intake, food craving and hunger. Furthermore, the project will provide the unique&#xD;
      opportunity to investigate novel mechanisms of insulin resistance in participants who have&#xD;
      been extensively metabolically characterized.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives The overarching aim of the study is to stimulate the hypothalamus-cognitive brain&#xD;
      network to improve insulin sensitivity and eating behavior.&#xD;
&#xD;
      Specific Objectives&#xD;
&#xD;
        1. Implement tDCS stimulation compared to sham stimulation in overweight and obese adults&#xD;
           to assess the impact on eating behavior, cognition and metabolism.&#xD;
&#xD;
        2. Evaluate whether 3-day non-invasive brain stimulation of the hypothalamus-cognitive&#xD;
           network has a causal effect on metabolism.&#xD;
&#xD;
        3. Evaluate whether 3-day non-invasive brain stimulation has a significant effect on brain&#xD;
           functional connectivity and diffusion parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 26, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2023</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>Peripheral insulin sensitivity</measure>
    <time_frame>1 day after last intervention tDCS day</time_frame>
    <description>Oral glucose tolerance derived insulin sensitivity based on the Matsuda index</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Caloric intake (kcal)</measure>
    <time_frame>1 hour directly after tDCS stimulation</time_frame>
    <description>Free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in subjective feeling of hunger and food craving</measure>
    <time_frame>5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet</time_frame>
    <description>On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using a questionnaire.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Performance during stop-signal task</measure>
    <time_frame>task is performed during 20-minutes tDCS stimulation</time_frame>
    <description>Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tastiness and healthiness rating of food stimuli</measure>
    <time_frame>task is performed immediatly after buffet</time_frame>
    <description>Using a computer based task, participants rate food pictures of low caloric and high caloric foods and snacks on a 5-point scale based on subjective tastiness and healthiness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food choice</measure>
    <time_frame>task is performed immediatly after buffet</time_frame>
    <description>Using a computer based task, participants have to choose food items they preferred to eat compared to a reference food on a 5-point choice scale. The reference (or &quot;neutral&quot;) food item is individually determined based the health and taste rating [Scale: 1= not tasty/ not healthy up to 5= very tasty/ very heahlty].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional connectivity</measure>
    <time_frame>10 minutes functional MRI measurement performed before and after three day tDCS stimulation</time_frame>
    <description>Resting-state functional connectivity of the hypothalamus-cognitive network is assessed by functional magnetic resonance imaging (fMRI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diffusion-weighted imaging</measure>
    <time_frame>15 minutes MRI measurement performed before and after three day tDCS stimulation</time_frame>
    <description>Diffusion weighted parameter based on MRI measurements</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Transcranial Direct Current Stimulation</condition>
  <condition>Obesity</condition>
  <condition>Diabetes</condition>
  <condition>Magnetic Resonance Imaging</condition>
  <arm_group>
    <arm_group_label>Anodal tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anodal tDCS of the hypothalamus-cognitive network</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cathodal tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cathodal tDCS of the hypothalamus-cognitive network</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Single blind sham stimulation (ramp-up ramp-down stimulation will be applied for 30 seconds in order to simulate the active condition without any further continuous administration of current)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>transcranial direct current stimulation</intervention_name>
    <description>anodal or cathodal transcranial direct current stimulation</description>
    <arm_group_label>Anodal tDCS</arm_group_label>
    <arm_group_label>Cathodal tDCS</arm_group_label>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) between 25.5 and 39.5 kg/m2&#xD;
&#xD;
          -  Age between 20 to 66 years of age&#xD;
&#xD;
          -  Waist circumference &gt; 80 cm for women, &gt; 94 cm for men&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Insufficient knowledge of the German language&#xD;
&#xD;
          -  Persons who cannot legally give consent&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  History of severe mental or somatic disorders including neurological diseases (incl.&#xD;
             epileptic seizures)&#xD;
&#xD;
          -  Taking psychotropic drugs&#xD;
&#xD;
          -  Previous bariatric surgery&#xD;
&#xD;
          -  Acute infection within the last 4 weeks&#xD;
&#xD;
          -  Hemoglobin values less than 12g/dl for women, less than 14 g/dl for men&#xD;
&#xD;
          -  Current participation in a lifestyle intervention study or a pharmaceutical study&#xD;
&#xD;
          -  Contradictions to a MRI measurement (e.g. metal implants)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>66 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephanie Kullmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy of Tübingen, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Clinic Tübingen</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</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>
  <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/NCT04420650
org study id: BRAINSTIM
nct id: NCT04420650
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Efforts in curing and preventing obesity and type 2 diabetes (T2D) have been elusive thus
      far. One reason for that is the lack of understanding of the role of the brain in the
      development and treatment of the disease. In recent studies, the hypothalamus was identified
      as part of a brain network including higher cognitive regions that is particularly vulnerable
      to insulin resistance. Furthermore, the central insulin response in this network predicted
      food craving and hunger. In this project, transcranial direct current stimulation (tDCS) is
      implemented as a tool to stimulate brain networks. The investigators hypothesize that
      stimulating the hypothalamus-cognitive network will enhance insulin sensitivity and reduce
      food intake, food craving and hunger. Furthermore, the project will provide the unique
      opportunity to investigate novel mechanisms of insulin resistance in participants who have
      been extensively metabolically characterized.
Objectives The overarching aim of the study is to stimulate the hypothalamus-cognitive brain
      network to improve insulin sensitivity and eating behavior.

      Specific Objectives

        1. Implement tDCS stimulation compared to sham stimulation in overweight and obese adults
           to assess the impact on eating behavior, cognition and metabolism.

        2. Evaluate whether 3-day non-invasive brain stimulation of the hypothalamus-cognitive
           network has a causal effect on metabolism.

        3. Evaluate whether 3-day non-invasive brain stimulation has a significant effect on brain
           functional connectivity and diffusion parameters.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Peripheral insulin sensitivity
time frame: 1 day after last intervention tDCS day
description: Oral glucose tolerance derived insulin sensitivity based on the Matsuda index
measure: Caloric intake (kcal)
time frame: 1 hour directly after tDCS stimulation
description: Free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented.
measure: Change in subjective feeling of hunger and food craving
time frame: 5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet
description: On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using a questionnaire.
measure: Performance during stop-signal task
time frame: task is performed during 20-minutes tDCS stimulation
description: Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT).
measure: Tastiness and healthiness rating of food stimuli
time frame: task is performed immediatly after buffet
description: Using a computer based task, participants rate food pictures of low caloric and high caloric foods and snacks on a 5-point scale based on subjective tastiness and healthiness.
measure: Food choice
time frame: task is performed immediatly after buffet
description: Using a computer based task, participants have to choose food items they preferred to eat compared to a reference food on a 5-point choice scale. The reference (or "neutral") food item is individually determined based the health and taste rating [Scale: 1= not tasty/ not healthy up to 5= very tasty/ very heahlty].
measure: Functional connectivity
time frame: 10 minutes functional MRI measurement performed before and after three day tDCS stimulation
description: Resting-state functional connectivity of the hypothalamus-cognitive network is assessed by functional magnetic resonance imaging (fMRI)
measure: Diffusion-weighted imaging
time frame: 15 minutes MRI measurement performed before and after three day tDCS stimulation
description: Diffusion weighted parameter based on MRI measurements
arm group label: Anodal tDCS
arm group type: Active Comparator
description: Anodal tDCS of the hypothalamus-cognitive network
arm group label: Cathodal tDCS
arm group type: Active Comparator
description: Cathodal tDCS of the hypothalamus-cognitive network
arm group label: Sham Stimulation
arm group type: Sham Comparator
description: Single blind sham stimulation (ramp-up ramp-down stimulation will be applied for 30 seconds in order to simulate the active condition without any further continuous administration of current)
intervention type: Device
intervention name: transcranial direct current stimulation
description: anodal or cathodal transcranial direct current stimulation
arm group label: Anodal tDCS
arm group label: Cathodal tDCS
arm group label: Sham Stimulation
criteria: 
gender: All
minimum age: 20 Years
maximum age: 66 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephanie Kullmann, PhD
role: Principal Investigator
affiliation: Univeristy of Tübingen, Germany
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Insulin Resistance
sharing ipd: No