Liver-enriched Antimicrobial Peptide 2

A Leap to Understand Glucoregulatory Effects of Liver-enriched Antimicrobial Peptide 2 (LEAP-2)

The investigators aim to investigate the physiological importance of LEAP-2 in healthy volunteers focusing on its potential insulinotropic effects.

Study Overview

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

Detailed Description

The dramatic and almost immediate effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes (T2D) can only in part be explained by alterations in the plasma concentrations of known peptides. Thus, other - yet unknown - signals or hormones elicited from the endocrine cells of the small intestine may play an important role for the remission of T2D observed following RYGB. In a recent study, a predicted sequence of liver-enriched antimicrobial peptide 2 (LEAP-2) was shown to induce a glucose-stimulated insulin secretion in isolated human pancreatic islets. The fragment was subsequently identified to be circulating in human plasma in concentrations comparable to the circulating levels of other known gut secreted hormones, hereby validating that LEAP-2 is an endogenous circulating peptide.

The investigators hypothesise that LEAP-2 increases insulin secretion during a graded glucose infusion as assessed by plasma insulin and C-peptide compared with saline (placebo) in healthy subjects. The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days and ten young healthy male participants. The co-primary endpoints are the difference in plasma insulin levels during a graded glucose infusion and beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration between the two study days with either saline (placebo) or LEAP-2 infusion.

• Study Type: Interventional
• Enrollment (Actual): 10
• 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 20-25 kg/m2
• Informed consent

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• ALAT and/or ASAT >2 times normal values or history of hepatobiliary and/or gastrointestinal disorder(s)
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses
• Any ongoing medication that the investigator evaluates would interfere with trial participation.
• First- and second-degree relatives with diabetes
• Regular tobacco smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Saline	Other: Placebo; Saline
EXPERIMENTAL: LEAP-2; Liver-enriched antimicrobial peptide 2	Biological: Liver-enriched antimicrobial peptide 2; Infusion of LEAP-2 during a 180 min grated glucose infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma insulin	Difference in plasma insulin levels	-45 to 180 minutes
Beta-cell secretion	Beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration	-45 to 180 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LEAP-2	Plasma concentrations of LEAP-2	-45 to 210 minutes
Resting energy expenditure	Changes in resting energy expenditure using indirect calorimetry	-20 to 160 minutes
Appetite, satiety, and general well-being	Appetite, satiety, and general well-being assessed by visual analogue scale (VAS)	-45 to 210 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: Gubra ApS
• Investigators: Study Director: Filip K Knop, MD, PhD, University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 28, 2019
• Primary Completion (ACTUAL): May 20, 2019
• Study Completion (ACTUAL): May 20, 2019

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (ACTUAL): August 2, 2019

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: LEAP-2

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