<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/NCT03290846</url>
  </required_header>
  <id_info>
    <org_study_id>T153/2016</org_study_id>
    <nct_id>NCT03290846</nct_id>
  </id_info>
  <brief_title>Secretin Activates Human Brown Fat and Induces Satiation.</brief_title>
  <acronym>GUTBAT</acronym>
  <official_title>Secretin Increases Glucose Uptake in Human Brown Adipose Tissue and Induces Satiation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Turku University Hospital</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>
      15 healthy males will be studied with PET/CT, using FDG to investigate glucose metabolism,&#xD;
      and radiowater to investigate perfusion. One scan will be performed in controlled cold&#xD;
      exposure, to see whether subjects have cold activated brown adipose tissue. Two scans will be&#xD;
      performed in room temperature conditions, where all subjects are blinded and randomised to&#xD;
      receive placebo and secretin hydrochloride. PET/CT scans will be analysed blinded.&#xD;
&#xD;
      20 healthy males will also be studied with fMRI, in order to investigate brain activity&#xD;
      responses to appetizing versus bland foods. This study will be conduced on the same patients&#xD;
      as the PET/CT study, but additional subjects with same inclusion and exclusion criteria will&#xD;
      be recruited. Two fMRI scans will be performed in room temperature conditions, where all&#xD;
      subjects are blinded and randomised to receive placebo and secretin hydrochloride. fMRI scans&#xD;
      will be analysed blinded.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The PET/CT study will consist of 15 healthy, normal weight males, between ages 18-65. A&#xD;
      2-hour oral glucose tolerance test is performed on screening day. Calorimetry data is&#xD;
      collected at baseline (resting and fasting) condition.&#xD;
&#xD;
      Three PET/CT scans on three different days will be performed to all 15 study subjects.&#xD;
      Radiowater (15O)-H2O is used to study perfusion and FDG ((F18)-FDG) to study glucose&#xD;
      metabolism. After radiowater, PET data is collected from the neck area for 6 minutes. After&#xD;
      FDG, PET data is collected for 40 minutes on the neck area, 15 minutes on the chest, 15&#xD;
      minutes on the abdomen and 15 minutes on the brain. Calorimetry is collected during the&#xD;
      entire scan. Blood samples are collected during scans for metabolites and for a plasma&#xD;
      activity curve.&#xD;
&#xD;
      One scan is performed during controlled, cold exposure. This is done to investigate, whether&#xD;
      patients have cold activated brown adipose tissue. After this, subjects will undergo two room&#xD;
      temperature condition scans on different days, where participants are single-blinded and&#xD;
      randomised to receive placebo (saline) or secretin (secretin hydrochloride) infusions. All&#xD;
      scans are done in fasting conditions. After subjects have fed at the PET centre, calorimetry&#xD;
      data is collected on all days.&#xD;
&#xD;
      A full body MRI will be performed on a separate day with the Dixon-method.&#xD;
&#xD;
      After scanning visits, brown adipose tissue biopsies will be taken from volunteers by a&#xD;
      plastic surgeon. These samples are analysed in Munich.&#xD;
&#xD;
      Dynamic scan data is analysed with the Carimas program, using Patlak plot. Analysis is&#xD;
      performed blinded. Further statistics analysis is done with SPSS.&#xD;
&#xD;
      The fMRI study will consist of 20 healthy, normal weight males, between ages 18-65. Subjects&#xD;
      who underwent PET/CT scanning will be recruited for this study, as well as an additional&#xD;
      group of subjects with the same inclusion and exclusion criteria. A 2-hour oral glucose&#xD;
      tolerance test is performed on screening day for additional subjcts.&#xD;
&#xD;
      Two fMRI scans are conducted in room temperature after overnight fast on separate days.&#xD;
      Subjects are randomized and blinded to receive placebo and secretin hydrochloride on separate&#xD;
      days. Data on brain activity while viewing appetizing versus bland food images is collected&#xD;
      during scan. After scanning subjects are given a meal and then followed up for two hours.&#xD;
      Data on subjective satiety will be collected with a visual analogue scale questionnaire on&#xD;
      nine different timepoints during the day: in preprandial, prandial and postprandial&#xD;
      conditions.&#xD;
&#xD;
      Functional MRI data is analyzed with Matlab. Analysis is performed blinded. Satiety score is&#xD;
      analzed with SPSS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2, 2016</start_date>
  <completion_date type="Actual">November 30, 2019</completion_date>
  <primary_completion_date type="Actual">October 30, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single blinded randomised study, secretin infusion is given on one day, saline infusion on an other day.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants receive drug and placebo infusion without knowing which day is which.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Secretin activates brown fat</measure>
    <time_frame>Effect within one hour</time_frame>
    <description>Secretin increases brown adipose tissue glucose uptake compared to placebo. This is studied with PET/CT, using a glucose tracer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Secretin activates brown fat</measure>
    <time_frame>Effect within six minutes</time_frame>
    <description>Secretin increases brown adipose tissue flow compared to placebo. This is studied with PET/CT, using a radiowater tracer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Secretin induces satiation</measure>
    <time_frame>Effect within one hour</time_frame>
    <description>Secretin attenuates brain activity, when subjects are viewing palatable vs. non-palatable food images.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secretin increases whole body energy expenditure</measure>
    <time_frame>Effect within two hours</time_frame>
    <description>Secretin increases whole body energy expenditure compared to placebo. Data is collected durin PET/CT scans by indirect calorimetry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secretin induces satiety</measure>
    <time_frame>Effect within three hours</time_frame>
    <description>Composite satiety score is measured by visual analogue scale questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secretin reduces food consumption.</measure>
    <time_frame>Within three days</time_frame>
    <description>Data on food consumption is collected directly after scan, as well as with food diaries. Calory intake is measured and comparisons are made between secretin and placebo.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Secretin induces changes in biomarkers and metabolites.</measure>
    <time_frame>Within two hours</time_frame>
    <description>Serum samples are collected during PET/CT scan and analyzed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Brown adipose tissue biopsies.</measure>
    <time_frame>Within 2 months</time_frame>
    <description>Brown adipose tissue biopsy samples are collected from subjects and analyzed.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Secretin study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PET and MRI scannings will be performed twice. Subjects will be given secretin hydrochloride and placebo on separate days. In addition, subjects will undergo cold exposure PET scanning once.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Secretin Human</intervention_name>
    <description>Randomized, single-blinded secretin hydrochloride infusion.</description>
    <arm_group_label>Secretin study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Solution</intervention_name>
    <description>Randomized, single-blinded saline infusion.</description>
    <arm_group_label>Secretin study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cold exposure</intervention_name>
    <description>All subjects will undergo a cold exposure PET scan.</description>
    <arm_group_label>Secretin study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  healthy normal weight&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cardiovascular disease, diabetes&#xD;
&#xD;
          -  smoking&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Radiation exposure for fertile women is avoided</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pirjo R Nuutila, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Turku UH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Turku PET Centre</name>
      <address>
        <city>Turku</city>
        <zip>20521</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>December 20, 2019</last_update_submitted>
  <last_update_submitted_qc>December 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Turku University Hospital</investigator_affiliation>
    <investigator_full_name>Pirjo Nuutila</investigator_full_name>
    <investigator_title>Professor, MD PhD</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Secretin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No data, where participants could be identifiable, will be shared.</ipd_description>
  </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/NCT03290846
org study id: T153/2016
nct id: NCT03290846
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
15 healthy males will be studied with PET/CT, using FDG to investigate glucose metabolism,
      and radiowater to investigate perfusion. One scan will be performed in controlled cold
      exposure, to see whether subjects have cold activated brown adipose tissue. Two scans will be
      performed in room temperature conditions, where all subjects are blinded and randomised to
      receive placebo and secretin hydrochloride. PET/CT scans will be analysed blinded.

      20 healthy males will also be studied with fMRI, in order to investigate brain activity
      responses to appetizing versus bland foods. This study will be conduced on the same patients
      as the PET/CT study, but additional subjects with same inclusion and exclusion criteria will
      be recruited. Two fMRI scans will be performed in room temperature conditions, where all
      subjects are blinded and randomised to receive placebo and secretin hydrochloride. fMRI scans
      will be analysed blinded.
The PET/CT study will consist of 15 healthy, normal weight males, between ages 18-65. A
      2-hour oral glucose tolerance test is performed on screening day. Calorimetry data is
      collected at baseline (resting and fasting) condition.

      Three PET/CT scans on three different days will be performed to all 15 study subjects.
      Radiowater (15O)-H2O is used to study perfusion and FDG ((F18)-FDG) to study glucose
      metabolism. After radiowater, PET data is collected from the neck area for 6 minutes. After
      FDG, PET data is collected for 40 minutes on the neck area, 15 minutes on the chest, 15
      minutes on the abdomen and 15 minutes on the brain. Calorimetry is collected during the
      entire scan. Blood samples are collected during scans for metabolites and for a plasma
      activity curve.

      One scan is performed during controlled, cold exposure. This is done to investigate, whether
      patients have cold activated brown adipose tissue. After this, subjects will undergo two room
      temperature condition scans on different days, where participants are single-blinded and
      randomised to receive placebo (saline) or secretin (secretin hydrochloride) infusions. All
      scans are done in fasting conditions. After subjects have fed at the PET centre, calorimetry
      data is collected on all days.

      A full body MRI will be performed on a separate day with the Dixon-method.

      After scanning visits, brown adipose tissue biopsies will be taken from volunteers by a
      plastic surgeon. These samples are analysed in Munich.

      Dynamic scan data is analysed with the Carimas program, using Patlak plot. Analysis is
      performed blinded. Further statistics analysis is done with SPSS.

      The fMRI study will consist of 20 healthy, normal weight males, between ages 18-65. Subjects
      who underwent PET/CT scanning will be recruited for this study, as well as an additional
      group of subjects with the same inclusion and exclusion criteria. A 2-hour oral glucose
      tolerance test is performed on screening day for additional subjcts.

      Two fMRI scans are conducted in room temperature after overnight fast on separate days.
      Subjects are randomized and blinded to receive placebo and secretin hydrochloride on separate
      days. Data on brain activity while viewing appetizing versus bland food images is collected
      during scan. After scanning subjects are given a meal and then followed up for two hours.
      Data on subjective satiety will be collected with a visual analogue scale questionnaire on
      nine different timepoints during the day: in preprandial, prandial and postprandial
      conditions.

      Functional MRI data is analyzed with Matlab. Analysis is performed blinded. Satiety score is
      analzed with SPSS.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single blinded randomised study, secretin infusion is given on one day, saline infusion on an other day.
primary purpose: Basic Science
masking: None (Open Label)
masking description: Participants receive drug and placebo infusion without knowing which day is which.
measure: Secretin activates brown fat
time frame: Effect within one hour
description: Secretin increases brown adipose tissue glucose uptake compared to placebo. This is studied with PET/CT, using a glucose tracer.
measure: Secretin activates brown fat
time frame: Effect within six minutes
description: Secretin increases brown adipose tissue flow compared to placebo. This is studied with PET/CT, using a radiowater tracer.
measure: Secretin induces satiation
time frame: Effect within one hour
description: Secretin attenuates brain activity, when subjects are viewing palatable vs. non-palatable food images.
measure: Secretin increases whole body energy expenditure
time frame: Effect within two hours
description: Secretin increases whole body energy expenditure compared to placebo. Data is collected durin PET/CT scans by indirect calorimetry.
measure: Secretin induces satiety
time frame: Effect within three hours
description: Composite satiety score is measured by visual analogue scale questionnaire
measure: Secretin reduces food consumption.
time frame: Within three days
description: Data on food consumption is collected directly after scan, as well as with food diaries. Calory intake is measured and comparisons are made between secretin and placebo.
measure: Secretin induces changes in biomarkers and metabolites.
time frame: Within two hours
description: Serum samples are collected during PET/CT scan and analyzed.
measure: Brown adipose tissue biopsies.
time frame: Within 2 months
description: Brown adipose tissue biopsy samples are collected from subjects and analyzed.
arm group label: Secretin study
arm group type: Experimental
description: PET and MRI scannings will be performed twice. Subjects will be given secretin hydrochloride and placebo on separate days. In addition, subjects will undergo cold exposure PET scanning once.
intervention type: Drug
intervention name: Secretin Human
description: Randomized, single-blinded secretin hydrochloride infusion.
arm group label: Secretin study
intervention type: Drug
intervention name: Saline Solution
description: Randomized, single-blinded saline infusion.
arm group label: Secretin study
intervention type: Other
intervention name: Cold exposure
description: All subjects will undergo a cold exposure PET scan.
arm group label: Secretin study
criteria: 
gender: Male
gender based: Yes
gender description: Radiation exposure for fertile women is avoided
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pirjo R Nuutila, MD,PhD
role: Principal Investigator
affiliation: Turku UH
facility: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: Turku University Hospital
investigator full name: Pirjo Nuutila
investigator title: Professor, MD PhD
mesh term: Secretin
sharing ipd: No
ipd description: No data, where participants could be identifiable, will be shared.