Effects of Antagonizing the Ghrelin Receptor on Brain Food Cue Reactivity in Obesity (LEAP2fMRI)

The naturally occurring peptide hormone liver-expressed antimicrobial peptide 2 (LEAP2) in an antagonist/inverse agonist towards the ghrelin receptor. Ghrelin administration has previously been shown to increase food cue reactivity in brain regions related to appetite and reward using functional MRI scans.

The aim of this clinical study is to investigate the effects of LEAP2 infusion on food cue reactivity in brain regions related to appetite and reward. Since LEAP2 is an antagonist/inverse agonist towards the ghrelin receptor we hypothesize, that LEAP2 infusion will decrease food cue reactivity in the above-mentioned regions compared to placebo infusion.

Participants with obesity (BMI 30-50 kg/m2) will be included and complete two experimental days with either LEAP2 or placebo infusion in a randomized crossover manner. On experimental days, participants will undergo a MRI scan with functional and anatomical modalities.

The study will attribute to gain a deeper understanding of the ghrelin system and its interaction with appetite regulation.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity and Overweight
• Intervention / Treatment: Other: LEAP2 infusion; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 60 years at the time of inclusion
• Body mass index 30-50 kg/m2
• Men
• Informed consent

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or present hepatobiliary and/or gastrointestinal disorder(s)
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Glycated haemoglobin (HbA1c) ≥48 mmol/mol and/or type 2 diabetes requiring medical treatment
• Regular tobacco smoking or use of other nicotine-containing products
• Claustrophobia
• 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: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo infusion	Other: Placebo; Placebo infusion (saline) is different from the LEAP2 infusion
Active Comparator: LEAP2 infusion	Other: LEAP2 infusion; The LEAP2 infusion is a hormone infusion that is different from the placebo (saline) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in food cue reactivity between experimental days	The primary endpoint is the change in BOLD signals when viewing pictures of food vs. non-food. Differences will be compared between the two experimental days with infusion of placebo and LEAP2, respectively.	time 75 - 135 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in peptide hormone concentrations	Plasma/serum concentrations of LEAP2, growth hormone as well as other glucose- and appetite-regulating gut hormones	From baseline to end of infusion
Difference in appetite ratings	Difference in visual Analogue Scales (VASs) assessing appetite, satiety, and hunger sensations.	From baseline to end of infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactivity from Negative Emoition Reactivity Test (NERT)	Change in BOLD signals when viewing pictures of that could cause stress (Negative Emoition Reactivity Test (NERT)). Differences will be compared between the two experimental days with infusion of placebo and LEAP2, respectively.	time 75 - 135 minutes
Plasma glucose	Change in plasma glucose concentration during the experimental days	Through experimental day. From timepoints -15 to 135 min

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Actual): March 3, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: H-2306418; NNF23OC0084114 (Other Grant/Funding Number: Novo Nordisk Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No