LEAP2 on Postprandial Glucose Metabolism and Food Intake n Obese Males

Obesity Clinical Trial

— LEAP2-OBCT  

Official title:

LEAP2 on Postprandial Glucose Metabolism and Food Intake in Obese Males

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05603598
• Other study ID #: H-19038628
• Status: Recruiting
• Phase: N/A
• Start date: August 24, 2022
• Est. completion date: May 1, 2023

Study information

• Verified date: October 2022
• Source: University Hospital, Gentofte, Copenhagen
• Contact: Anders Englund, MD
• Phone: +4530541484
• Email: anders.englund[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in obese volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in obese subjects.

Description:

In a recent study, the molecular phenotype of enteroendocrine cells in the small intestine before and after Roux-en-Y Gastric Bypass (RYGB) surgery in obese individuals was examined. Enteroendocrine cells were identified and isolated from intestinal biopsies and analysed for differentially expressed genes by Illumina High Throughput RNA-sequencing. It was discovered that the gene encoding liver-enriched antimicrobial peptide 2 (LEAP-2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP-2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP-2 peptide is identical in mice and humans. Thus, LEAP-2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction. Our group recently found a 12 % relative reduction in ad libitum food intake and reduced postprandial glucose excursions.

The present study hypothesis is that LEAP-2 alters postprandial glucose metabolism and decreases appetite as well as food intake in relation to a liquid mixed meal and a standardised ad libitum meal compared with saline (placebo) in obese subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Caucasian men

• Age between 18 and 25 years

• Body mass index between 30-50 kg/m2

• Informed consent

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)

• Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)

• Nephropathy (serum creatinine above normal range and/or albuminuria)

• Allergy or intolerance to ingredients included in the standardised meals

• First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol

• Regular tobacco smoking or use of other nicotine-containing products

• Any ongoing medication that the investigator evaluates would interfere with trial participation.

• Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• LEAP-2 Protein, Human
Intravenous infusion, mixed meal test, ad libitum meal test

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Gentofte Hospital	Hellerup	Capital Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Food intake, kilojoules	Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules of food eaten during the ad libitum meal.	290 to 320 minutes
Primary	Food intake, kilojoules per kilogram body weight	Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules per kilogram body weight of food eaten during the ad libitum meal.	290 to 320 minutes
Secondary	VAS, appetite	Visual analogue scales (VASs) assessing appetite (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)	-35 to 320 minutes
Secondary	VAS, satiety	Visual analogue scales (VASs) assessing satiety sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)	-35 to 320 minutes
Secondary	VAS, hunger	Visual analogue scales (VASs) assessing hunger sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)	-35 to 320 minutes
Secondary	VAS, thirst	Visual analogue scales (VASs) assessing thirst (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)	-35 to 320 minutes
Secondary	Alterations in gastric emptying	Paracetamol concentration in plasma after intake of 1.5 g paracetamol	-35 to 320 minutes
Secondary	Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration	Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration	-35 to 320 minutes
Secondary	Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones	Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones	-35 to 320 minutes
Secondary	Changes in resting energy expenditure (REE)	Changes in resting energy expenditure (REE) measured by indirect calorimetry	-35 to 320 minutes
Secondary	Triglyceride responses	Plasma triglyceride	-35 to 320 minutes
Secondary	Cholesterol responses	Plasma Cholesterol	-35 to 320 minutes
Secondary	Free fatty acid responses	Plasma Free fatty acid	-35 to 320 minutes