Protein Dose-repsonse Effect on GLP-1, PYY and Appetite in Male Subjects

Obesity Clinical Trial

— Protein  

Official title:

The Contribution of Gastrointestinal Appetite Hormones to Protein-induced

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01561235
• Other study ID #: B243
• Status: Completed
• Phase: N/A
• First received: March 13, 2012
• Last updated: June 20, 2012
• Start date: February 2008
• Est. completion date: July 2008

Study information

• Verified date: June 2012
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

Dietary protein appears to be the most satiating and thermogenic macronutrient. However, how protein exerts its effect on appetite is not fully known. The effect have been suggested to be related to a higher oxidation rate of protein compared to carbohydrate and fat, and also to a greater thermogenic effect causing greater increase in core temperature. The involvement of peripheral appetite-regulating hormones has only been sparingly investigated.

The objective is to investigate the satiating effects of meals with varying content of meat-based protein and whether a dose-response effect can be found on appetite-regulating hormones and appetite ratings.

Design: 25 men will participate in the 3-way, randomized, double-blind, crossover study. The test meals is isocaloric with 30E% fat and increasing protein content at the expense of carbohydrate. Test meals are: normal protein content (NP, 14E% protein), medium-high protein content (MHP, 25E%), and high protein content(HP, 50E%). Four-hour subjective appetite ratings and blood samples will be assessed every half-hour. Subsequently, the subjects will served an ad libitum lunch.

Description:

Dietary protein appears to be the most satiating and thermogenic macronutrient (7-11). However, how protein exerts its effect on appetite is not fully known. The effect have been suggested to be related to a higher oxidation rate of protein compared to carbohydrate and fat (12), and also to a greater thermogenic effect causing greater increase in core temperature (13). The involvement of peripheral appetite-regulating hormones has only been sparingly investigated (14). These studies have only included two preloads of different concentrations of protein. This is not an optimal design for investigating the protein dose-dependent effect as the threshold can have been reached in between the two concentrations. The effect of protein has mainly been investigated on glucagon-like peptide-1 (GLP-1), ghrelin, cholecystokinin (CCK), and generally after intake of protein below 35% of the energy content (35E%) (5;15-18). The relationship between these appetite-regulating hormones and appetite is still elusive due to contradicting results. Only one study has investigated the effect of protein preloads above 50E%. Bowen et al. (19) found that the high protein preloads could decrease the concentration of CCK and the rate of gastric emptying, which have been shown to enhance the satiating effect of food (20-22). Thus there is a need to examine the effect of protein on appetite-regulating hormones in a dose-response manner in order to detect whether there is an interaction between them and if they can be related to changes in subjective sensations of appetite and EI (14). This should be examined by comparing more than two isocaloric meals in which the protein content and one other macronutrient should vary whereas the third macronutrient should be kept fixed.

Thus, the objective of this study is to investigate the mechanisms responsible for the satiating effects of protein in three isocaloric test meals with a protein content of 14, 25 or 50 E% protein. A possible dose-response effect of protein is investigated on a number of appetite-regulating hormones/peptides, together with changes in ad libitum energy intake.

Design: 25 men will participate in the 3-way, randomized, double-blind, crossover study. The test meals is isocaloric with 30E% fat and increasing protein content at the expense of carbohydrate. Test meals are: normal protein content (NP, 14E% protein), medium-high protein content (MHP, 25E%), and high protein content(HP, 50E%). Four-hour subjective appetite ratings and blood samples will be assessed every half-hour. Subsequently, the subjects will served an ad libitum lunch.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy,

• BMI: 18.5-40 kg/m2,

• Weight stable (within +/- 3 kg) two months prior to study inclusion,

• Non-smoking,

• Nonathletic,

Exclusion Criteria:

• BMI > 40 kg/m2,

• Change in smoking status,

• Daily or frequent use of medication,

• Suffering from metabolic diseases,

• Suffering from psychiatric diseases,

• Suffering from any other clinical condition, which would make the subject unfit to participate in the study,

• Blood pressure was above 150/90 mmHg,

• Hemoglobin < 8 mmol/l.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Obesity

Intervention

Other:
• Dose-reponse effect of protein on appetite and appetite-regulating hormones
3-arm meal study for investigation of the mechanisms responsible for the satiating effects of protein in three isocaloric test meals with a protein content of 14, 25 or 50 E% protein. A possible 4-h dose-response effect of protein was investigated on a number of appetite-regulating hormones/peptides, together with changes in subjective appetite sensations and sensory desires were evaluated and ad libitum energy intake.

Locations

Country	Name	City	State
Denmark	Department of human Nutrition	Frederiksberg

Sponsors (1)

Lead Sponsor	Collaborator
University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute 4-h changes from baseline in the postprandial concentration of GLP-1	Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 30, 60, 90, 120, 150, 180, 240 minutes.; Blood samples are analyzed for GLP-1. Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed.	Measured on 3 seperate test days in a crossover design. Each test day was seperated by >4 weeks. On each test day GLP-1 was measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake	No
Secondary	Acute 4-h changes from baseline in subjective appetite sensations using visual analogue scales	Assessment of subjective appetite sensations (visual analogue scales (VAS)) at time 0 (baseline - prior to the test meal) and at time 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.; Measured subjective appetite sensations of hunger, satiety, prospective consumption, fullness, composite appetite score and sensory desires to something sweet, salty, rich in fat, or meat/fish.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day appetite sensations were measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.	No
Secondary	Acute 4-h changes from baseline in the postprandial concentration of appetite regulating hormones/peptides	Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 30, 60, 90, 120, 150, 180, 240 minutes.; Blood samples are or will be analyzed for glucagon, pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), peptid YY (PYY), ghrelin, CCK, amylin and apolipoprotein-IV.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.	No
Secondary	Acute 4-h changes from baseline in the postprandial concentration of glucose	Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes.; Blood samples was analyzed for glucose.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes post intake.	No
Secondary	Acute 4-h changes from baseline in the postprandial concentration of insulin	Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes.; Blood samples was analyzed for insulin.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes post intake.	No
Secondary	Acute 4-h changes from baseline in the postprandial concentrations of lipids	Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 30, 60, 90, 120, 150, 180, 240 minutes.; Blood samples were analyzed for triglycerides, free fatty acids (FFA), total cholesterol, HDL-cholesterol.; The concentration of low density lipoprotein (LDL) cholesterol will be estimated as described by Friedwald et al.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.	No
Secondary	Acute 4-h changes from baseline in the body temperature	Body temperature measurement were assessed at time 0, 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.; Temperature was measured in the participants' ears (ThermoScan 6022, Braun GmbH, Kronberg, Germany).; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day temperature was measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.	No
Secondary	Rate of gastric emptying (4-h change from baseline in postprandial concentration of paracetamol)	The subjects drank 500 mg paracetamol desolved in 100 ml water together with the test meal.; Blood samples were taken prior to the test meal (baseline). After initiation of the test meal blood samples were collected at time 30, 60, 90, 120, 150, 180, 240 minutes.; Blood samples was analyzed for concentration of paracetamol.; Data are planned to be statistically analyzed as repeated measurements in mixed linear models. Peak and time to peak will also be analyzed.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.	No
Secondary	Rating of the organoleptic quality of the test meals	After completion of the meal the subjects rated the organoleptic quality of the meal by visual analogue scales (VAS) in regard to appearance, smell, taste, after-taste, and general palatability of the meal.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the test meal (approximately) time 15 minutes post intake) subjects rated the test meals	No
Secondary	Rating of the organoleptic quality of the ad libitum meal	After completion of the meal the subjects rated the organoleptic quality of the ad libitum meal by visual analogue scales (VAS) in regard to appearance, smell, taste, after-taste, and general palatability of the meal.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the ad libitum meal subjects rated the meal	No
Secondary	Subjective appetite sensations (visual analogue scales) after ad libitum meal	After completion of the meal the subjects rated the subjective appetite sensations by visual analogue scales (VAS) in regard to sensation of hunger, satiety, prospective consumption, fullness, composite appetite score and sensory desires to eat something sweet, salty, rich in fat, or meat/fish.	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the ad libitum meal subjects rated their subjective sensation of appetite (approximately 4.5-h post intake of the test meal)	No
Secondary	ad libitum energy intake (EI)	240 min after each test meal an ad libitum meal was served, and the total energy intake was recorded	Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. EI was measured 240 min after intake of the test meal	No