Location Specific Differences in Intestinal Brake Activation

The Effect of Intestinal Brake Activation at Different Locations in the Gut on Food Intake and Hormone Release

The appearance of intact macronutrients in the small intestine can result in the activation of an intestinal brake; a negative feedback mechanism from different parts of the intestine to the stomach, the small intestine and to the central nervous system. These processes inhibit food processing, appetite sensations and food intake, and furthermore they increase feelings of satiety and satiation. The researchers will investigate the effects of intraduodenal, intrajejunal and intralileal infusion of casein (protein) on ad libitum food intake, satiation and in vivo release of the gut satiety peptides CCK, PYY and GLP-1 and glucose and insulin.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Satiety; Overeating; Ileal Brake
• Intervention / Treatment: Other: placebo; Other: Casein (in duodenum); Other: Casein (in jejunum); Other: Casein (in ileum)

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6003
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Based on medical history and previous examination, no gastrointestinal complaints can be defined.
• Age between 18 and 65 years. This study will include healthy adult subjects (male and female). Women must be taking contraceptives.
• BMI between 18 and 25 kg/m2)
• Weight stable over at least the last 6 months (≤5% weight change)

Exclusion criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator.
• Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing
• Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
• Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator)
• Dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic)
• Pregnancy, lactation
• Excessive alcohol consumption (>20 alcoholic consumptions per week)
• Smoking
• Blood donation within 3 months before the study period
• Self-admitted HIV-positive state
• Weight <60kg
• Evidence of casein or sucrose hypersensitivity
• Participation in any other study in which radiation was used, within 12 months before the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Tap water infusion in all three locations (duodenum, jejunum and ileum)	Other: placebo; infusion of tap water in all regions (duodenum, jejunum and ileum)
Experimental: Duodenum; Infusion of casein in duodenum	Other: Casein (in duodenum); infusion of protein in duodenum
Experimental: Jejunum; Infusion of casein in jejunum	Other: Casein (in jejunum); infusion of protein in jejunum
Experimental: Ileum; Infusion of casein in ileum	Other: Casein (in ileum); infusion of protein in ileum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure ad libitum food intake at the end of the test day	Food intake measurement in kcal	1 test day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS scores for hunger and satiety	Visual analogue scale for hunger and satiety in mm (0-100 mm scale)	1 test day
GI peptides	Measurement of GI peptide release during protein infusion (CCK, GLP-1, PYY, insulin and glucose)	1 test day

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: A Masclee, Prof. dr., Maastricht University Medical Center

Publications and helpful links

General Publications

• van Avesaat M, Ripken D, Hendriks HF, Masclee AA, Troost FJ. Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release. Int J Obes (Lond). 2017 Feb;41(2):217-224. doi: 10.1038/ijo.2016.196. Epub 2016 Nov 4.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Estimate): July 16, 2015
• Last Update Submitted That Met QC Criteria: July 14, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Body Weight; Overweight; Hyperphagia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: METC-14-3-006