Studying the Influence of LEAP2 on Integrated Endocrine Control of Eating During Semaglutide Treatment

NCT07171723 | Recruiting Phase 1

• 1 other identifier: H-25035700
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study investigates how blocking the hunger-related ghrelin receptor affects appetite and metabolism in individuals with obesity who are treated with semaglutide (a GLP-1 receptor agonist). LEAP2, a naturally occurring hormone that inhibits the ghrelin receptor, is used as the investigational compound. The objective of the study is to clarify how the ghrelin system functions when appetite is suppressed by semaglutide treatment. Participants will receive either LEAP2 or placebo during two experimental visits in a randomized, double-blind, crossover design. The investigators will assess food intake, appetite sensations, glucose metabolism, and hormonal responses. By examining the interaction between semaglutide and ghrelin signaling, the study aims to improve understanding of how multiple appetite-regulating systems interact and whether additional hunger signals remain active during GLP-1 treatment. The findings may inform the development of future treatments for individuals with obesity.

Conditions

Obesity &Amp; Overweight

Outcome Measures

Primary Outcomes (1)

• Food intake

  Difference in total energy intake during a standardized ad libitum meal. Energy intake will be quantified as kilojoules (kJ) and kJ per kilogram of body weight consumed during the meal

  290 to 310 minutes

Secondary Outcomes (5)

• Composite score of sensation of hunger, fullness (reverse corded) and prospective food intake.

  -30 to 290 minutes

• Gastric emptying

  -30 to 290 minutes

• Plasma concentrations of glucose

  -30 to 290 minutes

• Circulating levels of growth hormone and IGF-1

  -30 to 290 minutes

• Circulating levels of acyl-ghrelin

  -30 to 290 minutes

Other Outcomes (10)

• Sensation of nausea, thirst, and comfort

  -30 to 290 minutes

• Circulating levels of LEAP2, insulin, glucagon, and other hormones and signaling molecules regulating glucose metabolism, gastrointestinal motility, energy expenditure and eating behaviour

  -30 to 290 minutes

• Lipids and other metabolism markers

  -30 to 290 minutes

Study Arms (2)

LEAP2

EXPERIMENTAL

An intravenous infusion of LEAP2, an endogenous inverse agonist and competitive antagonist of the ghrelin receptor (GHSR), will be administered at 40 pmol/kg/min for 6 hours.

Biological: Liver-Expressed Antimicrobial Peptide 2 (LEAP2)

Placebo

PLACEBO COMPARATOR

An intravenous infusion of isotonic saline (placebo) will be administered for 6 hours

Other: Placebo (saline)

Interventions

Liver-Expressed Antimicrobial Peptide 2 (LEAP2) BIOLOGICAL

Continuous intravenous infusion of LEAP2 (Liver-Expressed Antimicrobial Peptide 2), an endogenous inverse agonist and competitive antagonist of the ghrelin receptor (GHSR), administered at 40 pmol/kg/min for 6 hours. LEAP2 inhibits ghrelin-mediated signaling involved in hunger regulation, gastric motility, and growth hormone secretion. This intervention enables investigation of the physiological relevance of ghrelin receptor activity during semaglutide-induced appetite suppression

LEAP2

Placebo (saline) OTHER

Continuous intravenous infusion of isotonic saline (0.9% sodium chloride) for 6 hours. This placebo comparator is used to match the volume, rate, and duration of the active intervention (LEAP2) in a randomized, double-blind, crossover design. The placebo enables assessment of the physiological effects of ghrelin receptor blockade by LEAP2 in individuals with obesity treated with semaglutide

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years old
• Body mass index (BMI) above ≥ 25 kg/m2
• Informed oral and written consent

You may not qualify if:

• Anaemia
• Alanine aminotransferase (ALAT) \> 2 times normal value
• History of hepatobiliary and/or gastrointestinal disorder
• Kidney disease (serum creatinine above normal range and/or urine albumin-creatinine ratio 30mg/g confirmed with two measurements)
• Any ongoing medication that investigator evaluates would interfere with study participation
• Any physical or psychological condition that investigators evaluate would interfere with study participation including any acute or chronic illnesses.
• Regular tobacco smoking and/or use of other nicotine products
• Glycated haemoglobin HbA1c \> 48 and/or type 1 or type 2 diabetes medical treatment
• Women of childbearing potential who are not using effective contraception
• Pregnancy or breastfeeding

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, 2900, Denmark

RECRUITING

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Christian Legart, MD

CONTACT

+4520891501; christian.legart.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Ph.d, Head of Department, Center for Clinical Metabolic Research

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 12, 2025
• Study Start: September 1, 2025
• Primary Completion: December 14, 2025
• Study Completion: February 1, 2026
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

DK (1)