Co-infusion of Neurotensin and GLP-1 Effects on Appetite and Food Intake.

Study Overview
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Brief Summary
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Co-infusion of Neurotensin and GLP-1 Effects on Appetite and Food Intake.

Detailed Description
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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.

Official Title
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Effect of Combination of the Gut Hormones Neurotensin and GLP-1 on Physiological Regulation of Appetite and Food Intake

Conditions
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Obesity

Intervention / Treatment
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* Other: Saline + saline
* Other: Neurotensin + saline
* Other: GLP-1 + saline
* Other: GLP-1 + Neurotensin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be studied on multiple occasions (4 days) in a randomised and double blinded fashion.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Saline+Saline<br> | Other: Saline + saline<br>* Double saline infusion followed by an ad libitum meal<br>|
| Other: Neurotensin+Saline<br> | Other: Neurotensin + saline<br>* Neurotensin + saline infusion followed by an ad libitum meal<br>|
| Other: GLP-1+Saline<br> | Other: GLP-1 + saline<br>* GLP-1 + saline infusion followed by an ad libitum meal<br>|
| Other: Neurotensin + GLP-1<br> | Other: GLP-1 + Neurotensin<br>* GLP-1 + Neurotensin infusion followed by an ad libitum meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ad-libitum food intake | 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. | 120 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite and gastrointestinal sensations | Using visual analogue scales (VAS) the effect of infusions and meals will be documented. Ad libitum meals will also be evaluated using VAS. | -60, -30, 0, 30, 60, 90, 120, 150 and 180 min | 
| Plasma glucose | Bed-side measurements of plasma glucose | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Neurotensin | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| GLP-1 | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Insulin | Serum analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| C-peptide | Serum analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Bile acids | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Ghrelin | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Peptide YY (PYY) | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Leptin | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Metabolomics | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 
| Proteomics | Plasma analysis | -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 165 and 180 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurotensin, Glucagon like peptide-1 (GLP-1)