Clinical trial NCT04621409: LEAP2 on Postprandial Glucose Metabolism and Food Intake
Official title: Effects of LEAP-2 on Postprandial Glucose Metabolism and Food Intake
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Obesity
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Food intake
timeFrame: 260 to 290 minutes
Secondary outcomes:
measure: VAS
timeFrame: -30 to 290 minutes
measure: Alterations in gastric emptying
timeFrame: -30 to 290 minutes
measure: Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration
timeFrame: -30 to 290 minutes
measure: Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones
timeFrame: -30 to 290 minutes
measure: Changes in resting energy expenditure (REE)
timeFrame: -30 to 290 minutes
measure: Assessment of nitrogen balance and protein breakdown in urine
timeFrame: -30 to 290 minutes
measure: Triglyceride responses
timeFrame: -30 to 290 minutes
measure: Cholesterol responses
timeFrame: -30 to 290 minutes
measure: Free fatty acid responses
timeFrame: -30 to 290 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research
Study officials:
affiliation: Center for Clinical Metabolic Research
name: Filip K Knop, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: