Obesity
Conditions
Keywords
Neurotensin, Glucagon like peptide-1 (GLP-1)
Brief summary
Co-infusion of Neurotensin and GLP-1 Effects on Appetite and Food Intake.
Detailed description
Neurotensin (NT), a gut hormone and neuropeptide, and GLP-1, as well a gut hormone, increases in circulation after bariatric surgery in rodents and humans and inhibit food intake in mice. Studies in rodents have shown that a GLP-1 receptor agonist and long acting neurotensin inhibit food intake. This study investigates whether the synergistic anorexic effects of neurotensin and GLP-1 agonism suggested by animal studies can be translated.
Interventions
OTHERSaline + saline
Double saline infusion followed by an ad libitum meal
OTHERNeurotensin + saline
Neurotensin + saline infusion followed by an ad libitum meal
OTHERGLP-1 + saline
GLP-1 + saline infusion followed by an ad libitum meal
OTHERGLP-1 + Neurotensin
GLP-1 + Neurotensin infusion followed by an ad libitum meal
Sponsors
Copenhagen University Hospital, Hvidovre
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants will not be informed of the nature of the infusion they are administered on any of the study days. The investigator will be provided with an infusion (either isotonic saline with humane serum albumine (HSA) or isotonic saline with HSA + neurotensin or isotonic saline with HSA + GLP-1) prepared by a designated colleague
Intervention model description
Participants will be studied on multiple occasions (4 days) in a randomised and double blinded fashion.
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Informed consent * Above 18 years of age * Normal hemoglobin concentration * 28\<BMI\<40 kg/m2
Exclusion criteria
* Diabetes mellitus * Truncal vagotomy * Resection of intestine (apart from appendectomy) * Tobaccos use * Nephropathy (serum-creatinin\>130 micromolar or/and albuminuria) * Liver disease (Alanine transaminase or/and aspartate transaminase\>2 times normal range.) * Treatment with medication that cannot be paused in 12 hours * Allergy towards latex or plastic * Bleeding disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ad-libitum food intake | 120 min | Neurotensin (NT), saline, GLP-1 and GLP-1+Neurotensin will be infused on four occasions in random order, double blinded. After 2h of infusion an ad libitum meal will be served. When the meal is completed food intake will be determined by weighing the leftovers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma glucose | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Bed-side measurements of plasma glucose |
| Neurotensin | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| GLP-1 | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Insulin | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Serum analysis |
| C-peptide | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Serum analysis |
| Appetite and gastrointestinal sensations | -60, -30, 0, 30, 60, 90, 120, 150 and 180 min | Using visual analogue scales (VAS) the effect of infusions and meals will be documented. Ad libitum meals will also be evaluated using VAS. |
| Ghrelin | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Peptide YY (PYY) | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Leptin | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Metabolomics | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Proteomics | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
| Bile acids | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | Plasma analysis |
Countries
Denmark
Contacts
Primary ContactBirgitte Holst, PhD, Professor
Backup ContactSten Madsbad, DMsc, Professor
Outcome results
None listed