LEAP2 on Postprandial Glucose Metabolism and Food Intake

Effects of LEAP-2 on Postprandial Glucose Metabolism and Food Intake

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Biological: Liver-enriched antimicrobial peptide 2; Biological: Placebo

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: liver-enriched antimicrobial peptide 2; IV infusion of LEAP2, approximately 5 hours	Biological: Liver-enriched antimicrobial peptide 2; IV infusion of LEAP2, approximately 5 hours
Placebo Comparator: Placebo; IV infusion of saline, approximately 5 hours	Biological: Placebo; IV infusion of saline, approximately 5 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food intake	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.	260 to 290 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS	Visual analogue scales (VASs) assessing appetite, satiety and hunger sensations (from 0 to 10 cm on a scale = from mimimum to maximum sensation)	-30 to 290 minutes
Alterations in gastric emptying	Paracetamol concentration in plasma after intake of 1.5 g paracetamol	-30 to 290 minutes
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	-30 to 290 minutes
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	-30 to 290 minutes
Changes in resting energy expenditure (REE)	Changes in resting energy expenditure (REE) measured by indirect calorimetry	-30 to 290 minutes
Assessment of nitrogen balance and protein breakdown in urine	Urine concentrations of urea for assessment of nitrogen balance and protein breakdown	-30 to 290 minutes
Triglyceride responses	Plasma triglyceride	-30 to 290 minutes
Cholesterol responses	Plasma cholesterol	-30 to 290 minutes
Free fatty acid responses	Plasma free fatty acid	-30 to 290 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Filip K Knop, MD, PhD, Center for Clinical Metabolic Research

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): February 18, 2021
• Study Completion (Actual): February 18, 2021

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: LEAP2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No