Secretin Activates Human Brown Fat and Induces Satiation.
Condition: Obesity
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Secretin Human; Saline Solution; Cold exposure
Intervention type(s): Drug; Drug; Other
Intervention description(s): Randomized, single-blinded secretin hydrochloride infusion.; Randomized, single-blinded saline infusion.; All subjects will undergo a cold exposure PET scan.
Intervention MeSH terms: Secretin
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.
Masking: None (Open Label)
Primary purpose: Basic Science