LEAP2 Kinetics in Healthy Individuals

The Kinetics of LEAP2 in Man

The study aims to investigate the kinetics of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) 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

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 (LEAP2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP2 peptide is identical in mice and humans. Thus, LEAP2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction.

This study aims to investigate the kinetics of exogenous LEAP2 in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 8
• 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: Yes
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver-enriched antimicrobial peptide 2; IV infusion of LEAP2, 2 hours	Biological: Liver-enriched antimicrobial peptide 2; IV infusion of LEAP2, 2 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of LEAP2	Plasma concentrations of LEAP2	-30 to 270 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 270 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): May 24, 2021
• Primary Completion (Actual): June 25, 2021
• Study Completion (Actual): June 25, 2021

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 18, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

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

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