LEAP2 on Postprandial Glucose Metabolism and Food Intake n Obese Males (LEAP2-OBCT)

LEAP2 on Postprandial Glucose Metabolism and Food Intake in Obese Males

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: LEAP-2 Protein, Human

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. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anders Englund, MD; Phone Number: +4530541484; Email: anders.englund@regionh.dk

Study Locations

• Denmark
  • Capital Region
    • Hellerup, Capital Region, Denmark, 2900
      • Recruiting
      • Center for Clinical Metabolic Research, Gentofte Hospital
      • Contact: Filip K Knop, MD, professor; Phone Number: 004538674266; Email: filip.krag.knop.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; IV infusion of saline, approximately 5.5 hours	Drug: LEAP-2 Protein, Human; Intravenous infusion, mixed meal test, ad libitum meal test
Experimental: Liver-enriched antimicrobial peptide 2; IV infusion of LEAP2, approximately 5.5 hours	Drug: LEAP-2 Protein, Human; Intravenous infusion, mixed meal test, ad libitum meal test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Alterations in gastric emptying	Paracetamol concentration in plasma after intake of 1.5 g paracetamol	-35 to 320 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	-35 to 320 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	-35 to 320 minutes
Changes in resting energy expenditure (REE)	Changes in resting energy expenditure (REE) measured by indirect calorimetry	-35 to 320 minutes
Triglyceride responses	Plasma triglyceride	-35 to 320 minutes
Cholesterol responses	Plasma Cholesterol	-35 to 320 minutes
Free fatty acid responses	Plasma Free fatty acid	-35 to 320 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: October 19, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: H-19038628

Drug and device information, study documents

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