Obesity &Amp; OverweightEarly Phase 1SILENCEDNCT07171723
Studying the Influence of LEAP2 on Integrated Endocrine Control of Eating During Semaglutide Treatment
A Early Phase 1 study testing Liver-Expressed Antimicrobial Peptide 2 (LEAP2) in people with Obesity &Amp; Overweight, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity &Amp; Overweight
- What is being tested?
- Liver-Expressed Antimicrobial Peptide 2 (LEAP2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2025to 12 Aug 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 65 years old
- Body mass index (BMI) above ≥ 25 kg/m2
- Ongoing semaglutide treatment with a stable dose of ≥ 1 mg once weekly for a minimum of 3 months prior to inclusion
- Weight stability, defined as a maximum variation of ±3% between the highest and lowest recorded body weight during the 3 months prior to inclusion.
- Informed oral and written consent
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Gentofte Hospital
Hellerup, 2900
About this study
Official title: Effects of Antagonizing the Ghrelin Receptor in Individuals With Obesity on Treatment With Semaglutide
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.
Read the detailed description
This study investigates the physiological role of ghrelin receptor signaling in individuals with obesity receiving stable treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress appetite and induce weight loss. Ghrelin is the only known circulating orexigenic gut hormone, and its activity is mediated via the growth hormone secretagogue receptor (GHSR). Whether ghrelin signaling continues to contribute meaningfully to appetite regulation during pharmacological GLP-1 receptor activation remains unknown.
Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous inverse agonist and competitive antagonist of the GHSR. LEAP2 provides a highly specific and transient means of blocking ghrelin receptor activity in humans, enabling mechanistic exploration of its physiological relevance. Previous studies have demonstrated that LEAP2 infusion reduces ad libitum food intake and postprandial glucose excursions in both lean and obese individuals. However, the role of ghrelin signaling under conditions of GLP-1-induced appetite suppression has not been elucidated.
The SILENCED study is a randomized, double-blind, placebo-controlled, crossover trial. Twenty-four participants with obesity who are weight-stable and on a stable dose of ≥1 mg/week semaglutide for at least 3 months will complete two experimental study days. Each participant will receive a 6-hour intravenous infusion of either LEAP2 or placebo (saline) on separate days. During each visit, appetite-related measures, food intake, glucose metabolism, gastrointestinal motility, growth hormone levels, and energy expenditure will be assessed.
The primary outcome is total energy intake during a standardized ad libitum meal. Secondary and exploratory outcomes include visual analogue scale ratings of appetite, gastric emptying assessed via paracetamol absorption, postprandial glucose and hormone responses, and indirect calorimetry measurements.
This study is expected to provide novel insight into whether ghrelin receptor signaling continues to play a functional role in appetite and metabolism under pharmacological GLP-1 receptor activation. The findings may inform the development of future combination therapies targeting multiple appetite-regulating pathways in the treatment of obesity.
- Conditions
- Obesity &Amp; Overweight
- Being tested
- Liver-Expressed Antimicrobial Peptide 2 (LEAP2), Placebo (saline)
- Keywords
- LEAP2, Semaglutide
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Liver-Expressed Antimicrobial Peptide 2 (LEAP2) |
| Placebo | Placebo comparator | An intravenous infusion of isotonic saline (placebo) will be administered for 6 hours Receives: Other: Placebo (saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 290 to 310 minutes
Secondary outcomes (5)
Composite score of sensation of hunger, fullness (reverse corded) and prospective food intake.
Visual analogue scales (VASs) assessing appetite, satiety and hunger sensations (from 0 to 10 cm on a scale = from mimimum to maximum sensation)
Measured: -30 to 290 minutes
Gastric emptying
Paracetamol concentration in plasma after intake of 1.5 g paracetamol
Measured: -30 to 290 minutes
Plasma concentrations of glucose
Plasma glucose
Measured: -30 to 290 minutes
Circulating levels of growth hormone and IGF-1
Blood samples
Measured: -30 to 290 minutes
Circulating levels of acyl-ghrelin
Blood samples
Measured: -30 to 290 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start1 Sep 2025
- Primary completion12 Aug 2026
- Study completion12 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity &Amp; OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asger Lund, MD, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07171723
- Sponsor's protocol ID
- H-25035700
- Acronym
- SILENCED
- Status last verified
- Sep 2025
- First submitted
- 8 Sep 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Antagonizing the Ghrelin Receptor in Individuals With Obesity on Treatment With Semaglutide
- ClinicalTrials.gov ID
- NCT07171723
- Acronym / sponsor ID
- SILENCED / H-25035700
- Conditions
- Obesity &Amp; Overweight
- Keywords
- LEAP2, Semaglutide
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 12 Aug 2026 (actual)
- Study completion
- 12 Aug 2026 (actual)
- First posted
- 12 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study investigates the physiological role of ghrelin receptor signaling in individuals with obesity receiving stable treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress appetite and induce weight loss. Ghrelin is the only known circulating orexigenic gut hormone, and its activity is mediated via the growth hormone secretagogue receptor (GHSR). Whether ghrelin signaling continues to contribute meaningfully to appetite regulation during pharmacological GLP-1 receptor activation remains unknown.
Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous inverse agonist and competitive antagonist of the GHSR. LEAP2 provides a highly specific and transient means of blocking ghrelin receptor activity in humans, enabling mechanistic exploration of its physiological relevance. Previous studies have demonstrated that LEAP2 infusion reduces ad libitum food intake and postprandial glucose excursions in both lean and obese individuals. However, the role of ghrelin signaling under conditions of GLP-1-induced appetite suppression has not been elucidated.
The SILENCED study is a randomized, double-blind, placebo-controlled, crossover trial. Twenty-four participants with obesity who are weight-stable and on a stable dose of ≥1 mg/week semaglutide for at least 3 months will complete two experimental study days. Each participant will receive a 6-hour intravenous infusion of either LEAP2 or placebo (saline) on separate days. During each visit, appetite-related measures, food intake, glucose metabolism, gastrointestinal motility, growth hormone levels, and energy expenditure will be assessed.
The primary outcome is total energy intake during a standardized ad libitum meal. Secondary and exploratory outcomes include visual analogue scale ratings of appetite, gastric emptying assessed via paracetamol absorption, postprandial glucose and hormone responses, and indirect calorimetry measurements.
This study is expected to provide novel insight into whether ghrelin receptor signaling continues to play a functional role in appetite and metabolism under pharmacological GLP-1 receptor activation. The findings may inform the development of future combination therapies targeting multiple appetite-regulating pathways in the treatment of obesity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LEAP2 | Experimental | Biological: Liver-Expressed Antimicrobial Peptide 2 (LEAP2)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. |
| Placebo | Placebo comparator | Other: Placebo (saline)An intravenous infusion of isotonic saline (placebo) will be administered for 6 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 18 and 65 years old
- Body mass index (BMI) above ≥ 25 kg/m2
- Ongoing semaglutide treatment with a stable dose of ≥ 1 mg once weekly for a minimum of 3 months prior to inclusion
- Weight stability, defined as a maximum variation of ±3% between the highest and lowest recorded body weight during the 3 months prior to inclusion.
- Informed oral and written consent
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liver-Expressed Antimicrobial Peptide 2 (LEAP2)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 | Biological | LEAP2 |
| Placebo (saline)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 | Other | Placebo |
Primary outcome
Food intake
Time frame: 290 to 310 minutes
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
5 secondary outcomes
Composite score of sensation of hunger, fullness (reverse corded) and prospective food intake.
Time frame: -30 to 290 minutes
Gastric emptying
Time frame: -30 to 290 minutes
Plasma concentrations of glucose
Time frame: -30 to 290 minutes
Circulating levels of growth hormone and IGF-1
Time frame: -30 to 290 minutes
Circulating levels of acyl-ghrelin
Time frame: -30 to 290 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: 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
Related trials for Obesity &Amp; Overweight
RecruitingPhase 2
UBT251 Injection Phase II Clinical Study (CKD)
Obesity &Amp; Overweight, Chronic Kidney Disease
Active, not recruiting
E-Bike Commuting and Health in Overweight College Students
Obesity &Amp; Overweight, Sedentary Behaviors
Not yet recruiting
EAT SMART Teen Study
Obesity &Amp; Overweight
Active, not recruiting
Weight Loss and Endocrine Disrupting Chemicals (EDCs): Lifestyle Interventions to Lose Weight and Reduce EDC Exposure in Individuals With Overweight/Obesity
Obesity &Amp;Amp;Amp; Overweight, Environmental Exposure
Active, not recruiting
Can Gut Bacteria Predict Who Benefits Most From Exercise? A Gut Supplement to Help Exercise Non-Responders
Obesity &Amp; Overweight
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Liver-Expressed Antimicrobial Peptide 2 (LEAP2) in people with Obesity &Amp; Overweight, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Food intake (time frame: 290 to 310 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.