Neurotensin - an Important Regulator of Appetite in Humans?

Study Overview
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Brief Summary
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Neurotensin (NT) is a gut peptide released postprandially from the small intestine. It is known to exert a range of enterogastrone effects and in animal models it reduces food intake when administered by parenteral routes. This study investigates whether the anorexic effects of NT suggested by animal studies can be translated.

Official Title
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The Effect of Neurotensin on Appetite, Food Intake, Blood Glucose Regulation, Hormone Secretion, and the Degradation of Neurotensin in Vivo

Conditions
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Physiology - Regulation of Appetite and Food Intake

Intervention / Treatment
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* Other: Neurotensin
* Other: Saline
* Other: Ad libitum meal
* Other: Liquid meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age = or above 18 years normal haemoglobin levels male informed consent Exclusion Criteria: Diabetes mellitus (fasting plasma glucose or HbA1c) Familiy history of diabetes mellitus Intestinal disease (incl e.g. inflammatory bowel disease and malabsorbtion) Family history of inflammatory bowel disease Previous intestinal resection Body mass index (BMI) over 25 kg/m2 Smoker Nephropathy (S-creatinine> 130 μM) Liver disease (ALAT and/or ASAT > 2 × upper normal limit)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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 (5 days) in a randomised and double blinded fashion. One day will serve as an acclimatization day.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saline + ad libitum meal<br>This will serve as the placebo / control day for the NT + ad libitum meal study day. | Other: Saline<br>* Intravenous infusion of saline<br>Other: Ad libitum meal<br>* Participants will be served a large meal serving. They will be instructed to eat until they do not feel hungry anymore.<br>|
| Experimental: NT + ad libitum meal<br>Neurotensin (NT) infusion followed by an ad libitum meal to study the effect of NT on ad libitum food intake. | Other: Neurotensin<br>* Intravenous infusion of neurotensin<br>Other: Ad libitum meal<br>* Participants will be served a large meal serving. They will be instructed to eat until they do not feel hungry anymore.<br>|
| Experimental: Saline + liquid meal + ad libitum meal<br>Saline infusion followed a standardized liquid mixed meal followed by an ad libitum meal. This will serve as the placebo / control day for the NT + standardized liquid mixed meal + ad libitum meal study day. Investigating the effect of NT on the second meal effect. | Other: Saline<br>* Intravenous infusion of saline<br>Other: Ad libitum meal<br>* Participants will be served a large meal serving. They will be instructed to eat until they do not feel hungry anymore.<br>Other: Liquid meal<br>* A standardized mixed liquid meal will be ingested to stimulate endogenous peptide hormone release<br>|
| Experimental: NT + liquid meal + ad libitum meal<br>NT infusion followed a standardized liquid mixed meal followed by an ad libitum meal. This study day aims to study the effect of NT on the second meal effect. | Other: Neurotensin<br>* Intravenous infusion of neurotensin<br>Other: Ad libitum meal<br>* Participants will be served a large meal serving. They will be instructed to eat until they do not feel hungry anymore.<br>Other: Liquid meal<br>* A standardized mixed liquid meal will be ingested to stimulate endogenous peptide hormone release<br>|
| Experimental: Neurotensin<br>Acclimatization day | Other: Neurotensin<br>* Intravenous infusion of neurotensin<br>Other: Ad libitum meal<br>* Participants will be served a large meal serving. They will be instructed to eat until they do not feel hungry anymore.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ad libitum food intake (ad libitum days) | Neurotensin (NT) and saline will be infused on two occasions in random order, double blinded. After 1h of infusion an ad libitum meal will be served. When the meal is completed food intake will be determined by weighing the leftovers. | 60 min | 
| Ad libitum food intake (liquid meal + ad libitum days) | Neurotensin (NT) and saline will be infused on two occasions in random order, double blinded. 1h into the infusions a standardized liquid mixed meal will be ingested. After another 180 min an ad libitum meal will be served. When the meal is completed food intake will be determined by weighing the leftovers. | 240 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite and gastrointestinal sensations (ad libitum days) | Using visual analogue scales (VAS) the effect of infusions and meals will be documented. Ad libitum meals will also be evaluated using VAS. | -60, -15, 15, 30, 60, 90, 120 min | 
| Appetite and gastrointestinal sensations (liquid meal + ad libitum days) | Using visual analogue scales (VAS) the effect of infusions and meals will be documented. Ad libitum meals will also be evaluated using VAS. | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Plasma glucose (ad libitum days) | Bed-side measurements of plasma glucose | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Plasma glucose (liquid meal + ad libitum days) | Bed-side measurements of plasma glucose | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240 min | 
| Neurotensin (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Neurotensin (liquid meal + ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240 min | 
| Insulin (liquid meal + ad libitum days) | Serum analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Bile acids (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| bile acids (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Ghrelin (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Ghrelin (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Glucagon-like peptide-1 (GLP-1) (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Glucagon-like peptide-1 (GLP-1) (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Glucose-dependent insulinotropic polypeptide (GIP) (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Peptide YY (PYY) (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Paracetamol (liquid meal + ad libitum days) | Serum analyses | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Pancreatic polypeptide (PP) (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 
| Pancreatic polypeptide (PP) (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Cholecystokinin (CCK) (ad libitum days) | Plasma analysis | -60, -30, -15, -1, 0- , 15, 30, 45, 60, 75, 90, 105, 120 min | 
| Cholecystokinin (CCK) (liquid meal + ad libitum days) | Plasma analysis | -60, -15, 15, 60, 90, 120, 150, 180, 210, 240 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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food intake, appetite, obesity treatment, neurotensin, gastrointestinal, peptide