LEAP2 on Postprandial Glucose Metabolism and Food Intake

NCT ID: NCT04621409

Last Updated: 2021-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2021-02-18

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

liver-enriched antimicrobial peptide 2

IV infusion of LEAP2, approximately 5 hours

Group Type: EXPERIMENTAL

Liver-enriched antimicrobial peptide 2

Intervention Type: BIOLOGICAL

IV infusion of LEAP2, approximately 5 hours

Placebo

IV infusion of saline, approximately 5 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

IV infusion of saline, approximately 5 hours

Interventions

Liver-enriched antimicrobial peptide 2

IV infusion of LEAP2, approximately 5 hours

Intervention Type: BIOLOGICAL

Placebo

IV infusion of saline, approximately 5 hours

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

Professor, head of department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip K Knop, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Clinical Metabolic Research

Locations

Center for Clinical Metabolic Research

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

LEAP2

Identifier Type: -

Identifier Source: org_study_id