A Phase 1/2 interventional study of Liver-expressed antimicrobial peptide 2 and Placebo in Obesity & Overweight, sponsored by University Hospital, Gentofte, Copenhagen. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by University Hospital, Gentofte, Copenhagen · Phase 1/2, Interventional, and Other
This study investigates whether temporarily blocking the ghrelin receptor affects appetite and food intake in people with overweight or obesity. Ghrelin is a hormone that stimulates hunger; the researchers are using LEAP2, a naturally occurring hormone that blocks ghrelin's receptor, as a research tool to study what happens when ghrelin signaling is turned off for 24 hours.
The study is a randomized, double-blind, placebo-controlled crossover trial. Eighteen adults with overweight or obesity (BMI ≥25 kg/m², elevated body fat percentage) will each complete two 24-hour study visits, at least 7 days apart: one with a continuous LEAP2 infusion and one with a saline placebo infusion, in random order. Neither participants nor most study staff will know which treatment is given on which visit.
During each 24-hour visit, participants will receive a standardized liquid test meal followed by ad libitum (eat-until-comfortably-full) lunch, dinner, and breakfast meals, plus access to snacks. The main question the study aims to answer is whether LEAP2 reduces the total amount of food eaten over 24 hours compared to placebo. Additional measurements include blood glucose levels, subjective feelings of hunger and fullness (via questionnaires), stomach emptying rate, blood pressure and heart rate, and hormone levels (including growth hormone, FSH, and LH). Some participants will also undergo a small fat tissue biopsy to study how genes and proteins related to metabolism respond.
The results are expected to improve understanding of how ghrelin and LEAP2 regulate appetite and metabolism in people with obesity, which may inform future approaches to treating obesity and related metabolic conditions.
Ghrelin is the only known circulating gut hormone with an appetite-stimulating (orexigenic) effect, acting through the growth hormone secretagogue receptor to increase food intake, promote fat storage, influence glucose metabolism, stimulate growth hormone release, and accelerate gastric emptying. Because this receptor retains some activity independent of ghrelin binding, blocking it may reveal effects beyond simple hormone suppression. LEAP2 (liver-expressed antimicrobial peptide 2) is a naturally occurring hormone that acts as a competitive antagonist and inverse agonist at the ghrelin receptor, offering a specific tool to transiently block ghrelin signaling in humans. The investigators' group has previously shown that short-term LEAP2 infusion reduces ad libitum food intake and improves postprandial glucose excursions in both lean individuals and individuals with obesity. Whether these effects persist, or how they evolve, over a full 24-hour period of ghrelin receptor blockade has not been established, and this study is designed to address that gap.
Eligible participants will attend a screening visit including medical history, biometric measurements, bioelectrical impedance analysis of body composition, blood pressure and heart rate, a screening blood panel, and (for female participants) a urine pregnancy test. Food-related addictive behavior will be characterized using the Yale Food Addiction Scale 2.0 to describe the study population.
Each participant will complete two experimental days at the Center for Clinical Metabolic Research, Gentofte/Herlev Hospital, separated by a washout of at least 7 days; for female participants, both visits will be scheduled in the same phase of the menstrual cycle. Before each visit, participants follow a standardized pre-visit protocol: replicating the same self-selected evening meal, an overnight fast, and avoidance of alcohol, strenuous exercise, prolonged fasting, and excessive caloric intake in the preceding 48 hours. A continuous glucose monitor is applied at least 24 hours before each visit.
On each 24-hour visit day, two intravenous cannulas are placed (one for infusion, one for arterialized venous blood sampling). Following a supine baseline assessment, participants receive a continuous intravenous infusion of either LEAP2 (40 pmol/kg/min) or matching saline placebo, prepared and labeled by an unblinded staff member not otherwise involved in study procedures. At 45 minutes, a standardized liquid mixed meal containing paracetamol (used to track gastric emptying) is consumed. Standardized ad libitum lunch, dinner, and breakfast meals are offered at approximately 5, 11, and 23 hours after infusion start, with continuous access to a standardized snack buffet between meals; amounts consumed are determined by weighing food before and after each meal. A structured light-activity protocol (short walks after lunch and dinner) is included to standardize energy expenditure conditions.
Throughout each visit, the study collects blood and urine samples at predefined time points; hourly visual analogue scale (VAS) assessments of hunger, fullness, satiety, prospective food intake, nausea, thirst, and comfort (except during the nocturnal period); indirect calorimetry at baseline and before each meal to measure resting energy expenditure and substrate oxidation; and the Leeds Food Preference Questionnaire at baseline and before the lunch and breakfast meals to assess explicit and implicit food preferences. Blood pressure, heart rate, and continuous glucose values are monitored throughout. After the breakfast meal, a subcutaneous adipose tissue biopsy is obtained under local anesthesia for transcriptomic, proteomic, and histological analysis.
Statistical analyses will use linear mixed models with treatment and period as fixed effects and an unstructured covariance structure to account for repeated measurements and potential variance heterogeneity between interventions, consistent with ICH E9 statistical guidance for crossover trials. The primary analysis will compare 24-hour ad libitum caloric intake between LEAP2 and placebo; secondary endpoints will be adjusted for multiple testing using the Benjamini-Hochberg method; exploratory endpoints will be reported descriptively with confidence intervals without formal hypothesis testing. The sample size of 18 completers was calculated based on a within-subject standard deviation for 24-hour energy intake derived from the investigators' prior LEAP2 studies, targeting detection of a clinically relevant 800 kJ reduction with 80% power at a two-sided alpha of 0.05.
6,583 studies on the registry are indexed under Obesity; 1,718 are open to participants now.
This study's planned enrollment of 18 is below the median of 77 across 5,091 interventional studies indexed under Obesity.
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Exclusion Criteria:
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 24 hours.
Biological: Liver-expressed antimicrobial peptide 2
An intravenous infusion of isotonic saline (placebo) will be administered for 24 hours.
Other: Placebo
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 24 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 24 hours in individuals with overweight or obesity.
Continuous intravenous infusion of isotonic saline (0.9% sodium chloride) for 24 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 overweight or obesity.
Food intake
Difference in total energy intake during the standardized ad libitum meals. Energy intake will be quantified as kilojoules (kJ) during the 24 hours
Time frame: 24 hours
Total food intake/24 hours
kJ/kg body weight
Time frame: 24 hours
Total food intake/24 hours
Total food intakes, kcal/kg body weight
Time frame: 24 hours
Food intake lunch
Food intake lunch in kJ
Time frame: 5 hours after infusion start
Food intake dinner
Food intake dinner in kJ
Time frame: 11 hours after infusion start
Food intake breakfast
Food intake breakfast in kJ
Time frame: 23 hours after infusion start
Composite score of sensation of hunger
Composite score calculated as (hunger + prospective food intake + \[100 - fullness\] + \[100 - satiety\]) / 4 from 100 mm visual analog scales (0 = minimum, 100 = maximum sensation), reported as baseline-subtracted AUC excluding the nocturnal period. Unit: mm × min.
Time frame: 24 hours
Explicit liking (Leeds Food Preference Questionnaire)
Explicit liking for high-fat relative to low-fat foods.
Time frame: 24 hours
Postprandial plasma concentrations of glucose after liquid meal test
Postprandial plasma concentrations of glucose after liquid meal test (mmol/(L\*min))
Time frame: 45 mins to 5 hours
Snack intake
Energy intake from the ad libitum snack buffet (kJ)
Time frame: 24 hours
Energy intake at lunch relative to body weight
kJ/kg
Time frame: 5 hours after infusion start
Gastric emptying
Gastric emptying after the mixed meal, assessed by paracetamol absorption: baseline-subtracted AUC (mmol/(L x min))
Time frame: 45 min to 5 hours
Energy intake at dinner relative to body weight
kJ/kg
Time frame: 11 hours after infusion start
Energy intake at breakfast relative to body weight
kJ/kg
Time frame: 23 hours after infusion start
Snack energy intake relative to body weight
kJ/kg
Time frame: 24 hours
Explicit wanting (Leeds Food Preference Questionnaire)
Explicit wanting for high-fat relative to low-fat foods.
Time frame: 24 hours
Snack buffet food preference
Proportion of snack energy intake (kJ) from different snack sources
Time frame: 24 hours
Implicit wanting (Leeds Food Preference Questionnaire)
Implicit wanting for high-fat relative to low-fat foods.
Time frame: 24 hours
Gastric emptying
Gastric emptying after the mixed meal, assessed by paracetamol absorption. Peak plasma concentration (mmol/L)
Time frame: 45 min to 5 hours
Gastric emptying
Gastric emptying after the mixed meal, assessed by paracetamol absorption. Time to peak (min)
Time frame: 45 min to 5 hours
Growth hormone
Circulating concentration of growth hormone
Time frame: 24 hours
LH (luteinizing hormone)
Circulating concentration of LH
Time frame: 24 hours
Acyl-ghrelin
Circulating concentration of acyl-ghrelin
Time frame: 24 hours
Nausea
Nausea on visual analog scale (100 mm)
Time frame: 24 hours
LEAP2, insulin, glucagon and other appetite/glucose-related hormones
Circulating concentration of LEAP2, insulin, glucagon and other hormones and biomarkers of appetite and glucose metabolism.
Time frame: 24 hours
Lipids and metabolic biomarkers
Circulating concentration of lipids and other metabolic biomarkers
Time frame: 24 hours
Energy expenditure
Resting energy expenditure (kcal/day)
Time frame: 5, 11, 23 hours
Duration of ad libitum meals
Time spent eating at the ad libitum lunch, dinner and breakfast (minutes).
Time frame: 24 hours
Water intake during ad libitum meals
Total water consumed during ad libitum meals (mL).
Time frame: 24 hours
Urinary nitrogen excretion
Total nitrogen excretion (g) in 24-hour urine collection.
Time frame: 24 hours
Other metabolic, endocrine and inflammatory biomarkers
Circulating metabolites, hormones and inflammatory markers
Time frame: 24 hours
Subcutaneous adipose tissue profiling
Biopsy-based RNA sequencing (relative gene expression), proteomics (relative protein abundance) and histology (semi-quantitative score of adipocyte morphology and immune cell infiltration).
Time frame: At end of infusion (after breakfast, ~24 hours)
Systolic blood pressure
Systolic blood pressure (mmHg)
Time frame: 24 hours
Organ markers
Safety blood tests: ALAT, ASAT, amylase, creatinine/eGFR, carbamide and electrolytes (sodium, potassium, calcium).
Time frame: Baseline, 12 and 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Time to peak (min)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Baseline-subtracted AUC (mmol/(L × min))
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Peak value (mmol/L)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Time in ranges (min)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Mean 24-h glucose (mmol/L)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Standard deviation (mmol/L)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Postprandial excursion (Δ peak - pre-meal baseline, mmol/L)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Coefficient of variation (%)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Mean nocturnal glucose (mmol/L)
Time frame: 24 hours
Continuous glucose monitoring (CGM) glucose metrics
Nocturnal coefficient of variation (%)
Time frame: 24 hours
FSH (follicle-stimulating hormone)
Circulating concentration of FSH
Time frame: 24 hours
Insulin-like growth factor 1 (IGF-1)
Circulating concentration of IGF-1
Time frame: 24 hours
Comfort
Comfort on a visual analog scale (100 mm)
Time frame: 24 hours
Thirst
Thirst on a visual analog scale (100 mm)
Time frame: 24 hours
Hunger
Hunger on visual analog scale (100 mm)
Time frame: 24 hours
Fullness
Fullness on visual analog scale (100 mm)
Time frame: 24 hours
Prospective food intake
Prospective food intake on visual analog scale (100 mm).
Time frame: 24 hours
Diastolic blood pressure
Diastolic blood pressure (mmHg)
Time frame: 24 hours
Heart rate
Heart rate (bpm)
Time frame: 24 hours
Satiety
Satiety on visual analog scale (100 mm)
Time frame: 24 hours
Respiratory Exchange Ratio (RER)
The respiratory exchange ratio (VCO₂/VO₂)
Time frame: 5, 11, 23 hours
No study locations are listed for this record.
Plan to share: Undecided — At this stage, no final decision has been made regarding sharing of individual participant data (IPD). While sharing de-identified data could contribute to scientific transparency, reproducibility, and collaborative advancement in obesity and metabolic research, several factors must be considered. These include ethical and legal obligations related to participant confidentiality, the need for appropriate data-use agreements, and institutional policies on data governance. The possibility of sharing IPD will be revisited upon study completion, in alignment with sponsor requirements, ethical approvals, and journal publication policies.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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