LEAP2 on Postprandial Glucose Metabolism and Food Intake

Early Phase 1

Completed

• Conditions: Obesity

• Registration Number: NCT04621409
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

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

Detailed 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.

The 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 healthy subjects.

Study Timeline

• Study First Submitted: 2020-10-12
• Study First Submitted QC: 2020-11-03
• Study First Posted: 2020-11-09
• Study Start: 2020-11-17
• Primary Completion: 2021-02-18
• Study Completion: 2021-02-18
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-25
• Last Update Posted: 2021-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• Caucasian men
• Age between 18 and 25 years
• Body mass index between 20-35 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Food intake	260 to 290 minutes	Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules (kJ) and kJ/kg body weight of food eaten during the ad libitum meal.

Secondary Outcome Measures

Name	Time	Method
VAS	-30 to 290 minutes	Visual analogue scales (VASs) assessing appetite, satiety and hunger sensations (from 0 to 10 cm on a scale = from mimimum to maximum sensation)
Alterations in gastric emptying	-30 to 290 minutes	Paracetamol concentration in plasma after intake of 1.5 g paracetamol
Changes in resting energy expenditure (REE)	-30 to 290 minutes	Changes in resting energy expenditure (REE) measured by indirect calorimetry
Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration	-30 to 290 minutes	Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration
Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones	-30 to 290 minutes	Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones
Assessment of nitrogen balance and protein breakdown in urine	-30 to 290 minutes	Urine concentrations of urea for assessment of nitrogen balance and protein breakdown
Triglyceride responses	-30 to 290 minutes	Plasma triglyceride
Cholesterol responses	-30 to 290 minutes	Plasma cholesterol
Free fatty acid responses	-30 to 290 minutes	Plasma free fatty acid

Trial Locations

Locations (1)

Center for Clinical Metabolic Research; 🇩🇰 Hellerup, Denmark