The Role of Secretin on the Energy Homeostasis

Study Overview
=================
Brief Summary
-----------------
As of last year, new insight into the function of secretin was brought about as rodent studies showed secretin to possess potential body weight-regulating effects. In these studies, secretin was shown to increase non-shivering thermogenesis in brown adipose tissue (BAT), decrease meal size and promote meal discontinuation. The mechanisms behind these regulatory effect of secretin on energy homeostasis are unclear,

Detailed Description
-----------------
Secretin was - as the first hormone - identified in 19021, but was not isolated until the 1960s. Secretin is produced in and secreted form small intestinal S cells. In the 1970s, the primary endocrine effects of secretin were unequivocally confirmed, namely potentiation of bicarbonate and pepsin secretion from the pancreas as well as stimulation of bile production in the liver. In the 1990s, the biosynthesis of secretin was delineated and its receptor was discovered. In the 2000s the pancreatic regulation of intestinal pH was shown to be secretin-mediated. As of last year, new insight into the function of secretin was brought about as rodent studies showed secretin to possess potential body weight-regulating effects. In these studies, secretin was shown to increase non-shivering thermogenesis in brown adipose tissue (BAT), decrease meal size and promote meal discontinuation. The primary aim of this study is to evaluate the effect of a 5-hour intravenous infusion with the naturally occurring hormone secretin on ad libitum food intake (primary endpoint) compared to a double-blinded placebo (isotonic saline) infusion in 25 healthy young males.

Official Title
-----------------
The Role of Secretin on the Energy Homeostasis

Conditions
-----------------
Obesity, Metabolic Disease, Diabetes, Adiposity

Intervention / Treatment
-----------------
* Drug: Secretin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 75 years Body mass index between 18.5 and 27.5 kg/m2 Informed consent Body weight above 50 kg Exclusion Criteria: Anaemia (blood haemoglobin below normal range) Known liver disease and/or alanine aminotransferase and/or aspartate transaminase > 2 times upper normal values Nephropathy (serum creatinine above normal range and/or albuminuria) Clinically significant kidney function impairment or other laboratory findings leading to the diagnosis of clinically relevant disorders (thyroid dysfunction, anaemia etc) Any physical or psychological condition that the investigators feel would interfere with trial participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomised, double-blinded, placebo-controlled, cross-over study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Secretin<br> | Drug: Secretin<br>* Native hormone<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Saline<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Food intake on ad libitum meal | Kilojoule | 300 minutes | 
| Duration of ad libitum meal | Duration in minutes | 300 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Water intake during ad libitum meal | mL | 300 minutes | 
| resting energy expenditure | Indirect calorimetry of respiration | Baseline, 90 minutes and 270 minutes | 
| Supraclavicular Brown adipose activity | Evaluated by neck skin temperature assessed using a non-invasive thermal imaging camera) | -15 to 15 , 90 and 270 minutes | 
| Appetite and satiety sensations (assessed by VASs), | Visual analogue scales with a scale of 1-10 (Direction of scale varies) | Every 15 minutes after infusion, until time-point 90, hereafter every 30 minutes | 
| Heart rate | heart rate . | every 15 minutes from from -15 to 300 minutes | 
| systolic blood pressure | Systolic blood pressure | every 15 minutes from from -15 to 300 minutes | 
| Diastolic blood pressure | Diastolic blood pressures | every 15 minutes from from -15 to 300 minutes | 
| Gallbladder motility | Gallbladder motility measured by Ultrasound | Timepoint -30, 10,20,45,60,75,90,120,210,300 minutes |