Liver-enriched Antimicrobial Peptide 2

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04043065
• Other study ID #: LEAP-2
• Status: Completed
• Phase: Early Phase 1
• Start date: January 28, 2019
• Est. completion date: May 20, 2019

Study information

• Verified date: May 2021
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 20, 2019
• Est. primary completion date: May 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Biological:
• Liver-enriched antimicrobial peptide 2
Infusion of LEAP-2 during a 180 min grated glucose infusion.

Other:
• Placebo
Saline

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research	Hellerup

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	Gubra ApS

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma insulin	Difference in plasma insulin levels	-45 to 180 minutes
Primary	Beta-cell secretion	Beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration	-45 to 180 minutes
Secondary	LEAP-2	Plasma concentrations of LEAP-2	-45 to 210 minutes
Secondary	Resting energy expenditure	Changes in resting energy expenditure using indirect calorimetry	-20 to 160 minutes
Secondary	Appetite, satiety, and general well-being	Appetite, satiety, and general well-being assessed by visual analogue scale (VAS)	-45 to 210 minutes