Bariatric Surgery CandidateNCT05189353
The Importance of Ghrelin for Glucose Metabolism After Sleeve Gastrectomy
A study testing Ghrelin in people with Bariatric Surgery Candidate and Glucose Metabolism Disorders, run by Hvidovre University Hospital at 1 site in Denmark.
Trial summary
The overall aim is to delineate the contribution of ghrelin to glucose tolerance after sleeve gastrectomy. The hypothesis is that decreased concentration of ghrelin after SG is of importance for improved insulin secretion and glucose tolerance seen after SG. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bariatric Surgery Candidate, Glucose Metabolism Disorders
- What is being tested?
- Ghrelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteDenmark
- Study dates
- 14 Jan 2022to 26 Jun 2023
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Sleeve gastrectomy-operated > 12 months prior to inclusion
- Weight stable (+/- 3 kg during the last 3 months)
- Fasting glucose < 7,0 mmol/l / HbA1c < 48 mmol/mol pre- and postoperative
- Signed written informed consent
Who cannot join
- Pregnancy or breastfeeding.
- Haemoglobin < 6,5 mM.
Trial locations and contacts
1 site in 1 country.
About this study
The overall aim is to delineate the contribution of ghrelin to glucose tolerance after sleeve gastrectomy. The hypothesis is that decreased concentration of ghrelin after SG is of importance for improved insulin secretion and glucose tolerance seen after SG. The expectation is therefore that infusion of ghrelin will impair insulin secretion and glucose tolerance compared with a control day without ghrelin infusion.
Read the detailed description
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are bariatric procedures. Overwhelming evidence support bariatric surgery as the most effective treatment for severe obesity and related metabolic comorbidities, particularly type 2 diabetes mellitus.
The mechanisms of improved glycaemic control after SG are not fully understood and differ from those of RYGB. Interestingly, there is demonstrated a markedly lower secretion of the orexigenic hormone ghrelin after SG compared with both RYGB and unoperated obese controls. Hence, the decreased level of ghrelin could be of major importance in relation to the improved glucose tolerance after SG.
Ghrelin is secreted from the gastric mucosa in the fasting state and decreases in response to food intake. Administration of exogenous ghrelin reduces insulin sensitivity and glucose tolerance in healthy humans and contributes to hyperglycaemia. In accordance, ghrelin receptor knockout in mice improves glucose sensitivity and enhances glucose-stimulated insulin secretion.
On this background the investigators hypothesize that the markedly reduced secretion of ghrelin after SG could therefore be of particularly importance for the improved glucose tolerance after this procedure.
This present study is complementary to an on-going study in SG operated subjects, where the role of ghrelin for appetite and insulin secretion during a mixed meal followed by an ad libitum meal are investigated. In the present study the effect of ghrelin on insulin secretion and insulin sensitivity is thoroughly investigated using methods eliminating the effect of other hormones on glucose metabolism.
Ghrelin will be infused in physiological doses aiming for plasma concentration after SG resembling the pre-operative plasma concentrations.
Specific aim is to evaluate the effect of ghrelin on both alpha and beta cell function as well as on liver and peripheral insulin sensitivity in individuals with SG using matched controls. The subjects will be investigated with both glucose and glycerol tracers, IVGTT and a hyperinsulinemic euglycaemic clamp.
- Being tested
- Ghrelin, Placebo
- Keywords
- Ghrelin, Gastric sleeve, Glucose metabolism
- Medical subject headings
- Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GhrelinOther
Ghrelin infusion
PlaceboOther
Saline infusion
| Study group | Role | What they receive |
|---|---|---|
| Gastric sleeve operated | Experimental | 12 subjects with normal glucose tolerance (NGT) operated with SG minimum 12 month earlier Receives: Other: Ghrelin; Other: Placebo |
| Matched control group | Placebo comparator | 12 weight-matched unoperated subjects with NGT Receives: Other: Ghrelin; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in disposition index between the two study days with and without ghrelin in fusion in the SG operated group
The first phase insulin response will be related to the ambient insulin sensitivity by calculating the disposition index (FPIR x M-value).
Measured: 0-180 minutes
Secondary outcomes (2)
The difference in first phase insulin response (FPIR) between the two study days with and without ghrelin in fusion in the SG operated group
Estimation of beta-cell function, calculated from insulin secretion rate using c-peptid and deconvolution from 0-10 min.
Measured: 0-10 minutes (IVGTT)
The difference in Insulin sensitivity (M-value) between the two study days with and without ghrelin in fusion in the SG operated group
When a steady state is reached at the end of the clamp, the glucose infusion rate represents insulin-mediated glucose uptake by the body.
Measured: 160-180 minutes (the end of the clamp)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2022
- Study start14 Jan 2022
- Primary completion26 Jun 2023
- Study completion26 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bariatric Surgery CandidateStudies 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hvidovre University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Principal investigator, Marie-Louise Dichman, Hvidovre University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05189353
- Sponsor's protocol ID
- H-21037442
- Status last verified
- Oct 2023
- First submitted
- 28 Dec 2021
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dichman ML, Hedback N, London A, Jorgensen NB, Bojsen-Moller KN, Wewer Albrechtsen NJ, van Hall G, Kristiansen VB, Hartmann B, Holst JJ, Dirksen C, Svane MS, Madsbad S. The effect of ghrelin on insulin sensitivity and beta-cell function after sleeve gastrectomy. Am J Physiol Endocrinol Metab. 2026 Jul 1;331(1):E76-E86. doi: 10.1152/ajpendo.00065.2026. Epub 2026 Jun 1.
PubMed 42224086
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Importance of Ghrelin for Glucose Metabolism After Sleeve Gastrectomy
- ClinicalTrials.gov ID
- NCT05189353
- Acronym / sponsor ID
- H-21037442
- Keywords
- Ghrelin, Gastric sleeve, Glucose metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Hvidovre University HospitalUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 14 Jan 2022 (actual)
- Primary completion
- 26 Jun 2023 (actual)
- Study completion
- 26 Jun 2023 (actual)
- First posted
- 12 Jan 2022 (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.
The overall aim is to delineate the contribution of ghrelin to glucose tolerance after sleeve gastrectomy. The hypothesis is that decreased concentration of ghrelin after SG is of importance for improved insulin secretion and glucose tolerance seen after SG. The expectation is therefore that infusion of ghrelin will impair insulin secretion and glucose tolerance compared with a control day without ghrelin infusion.
Detailed description
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are bariatric procedures. Overwhelming evidence support bariatric surgery as the most effective treatment for severe obesity and related metabolic comorbidities, particularly type 2 diabetes mellitus.
The mechanisms of improved glycaemic control after SG are not fully understood and differ from those of RYGB. Interestingly, there is demonstrated a markedly lower secretion of the orexigenic hormone ghrelin after SG compared with both RYGB and unoperated obese controls. Hence, the decreased level of ghrelin could be of major importance in relation to the improved glucose tolerance after SG.
Ghrelin is secreted from the gastric mucosa in the fasting state and decreases in response to food intake. Administration of exogenous ghrelin reduces insulin sensitivity and glucose tolerance in healthy humans and contributes to hyperglycaemia. In accordance, ghrelin receptor knockout in mice improves glucose sensitivity and enhances glucose-stimulated insulin secretion.
On this background the investigators hypothesize that the markedly reduced secretion of ghrelin after SG could therefore be of particularly importance for the improved glucose tolerance after this procedure.
This present study is complementary to an on-going study in SG operated subjects, where the role of ghrelin for appetite and insulin secretion during a mixed meal followed by an ad libitum meal are investigated. In the present study the effect of ghrelin on insulin secretion and insulin sensitivity is thoroughly investigated using methods eliminating the effect of other hormones on glucose metabolism.
Ghrelin will be infused in physiological doses aiming for plasma concentration after SG resembling the pre-operative plasma concentrations.
Specific aim is to evaluate the effect of ghrelin on both alpha and beta cell function as well as on liver and peripheral insulin sensitivity in individuals with SG using matched controls. The subjects will be investigated with both glucose and glycerol tracers, IVGTT and a hyperinsulinemic euglycaemic clamp.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gastric sleeve operated | Experimental | Other: Ghrelin, Other: Placebo12 subjects with normal glucose tolerance (NGT) operated with SG minimum 12 month earlier |
| Matched control group | Placebo comparator | Other: Ghrelin, Other: Placebo12 weight-matched unoperated subjects with NGT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Sleeve gastrectomy-operated > 12 months prior to inclusion
- Weight stable (+/- 3 kg during the last 3 months)
- Fasting glucose < 7,0 mmol/l / HbA1c < 48 mmol/mol pre- and postoperative
- Signed written informed consent
Key exclusion criteria (2 listed)
- Pregnancy or breastfeeding.
- Haemoglobin < 6,5 mM.
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 |
|---|---|---|
| GhrelinGhrelin infusion | Other | Gastric sleeve operated, Matched control group |
| PlaceboSaline infusion | Other | Gastric sleeve operated, Matched control group |
Primary outcome
The difference in disposition index between the two study days with and without ghrelin in fusion in the SG operated group
Time frame: 0-180 minutes
The first phase insulin response will be related to the ambient insulin sensitivity by calculating the disposition index (FPIR x M-value).
2 secondary outcomes
The difference in first phase insulin response (FPIR) between the two study days with and without ghrelin in fusion in the SG operated group
Time frame: 0-10 minutes (IVGTT)
The difference in Insulin sensitivity (M-value) between the two study days with and without ghrelin in fusion in the SG operated group
Time frame: 160-180 minutes (the end of the clamp)
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 1 Nov 2023.
- Derived from this study: PubMed 42224086Dichman ML, Hedback N, London A, Jorgensen NB, Bojsen-Moller KN, Wewer Albrechtsen NJ, van Hall G, Kristiansen VB, Hartmann B, Holst JJ, Dirksen C, Svane MS, Madsbad S. The effect of ghrelin on insulin sensitivity and beta-cell function after sleeve gastrectomy. Am J Physiol Endocrinol Metab. 2026 Jul 1;331(1):E76-E86. doi: 10.1152/ajpendo.00065.2026. Epub 2026 Jun 1.
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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 study testing Ghrelin in people with Bariatric Surgery Candidate and Glucose Metabolism Disorders, run by Hvidovre University Hospital 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 4 inclusion and 2 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 1 Nov 2023. 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.
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?
The difference in disposition index between the two study days with and without ghrelin in fusion in the SG operated group (time frame: 0-180 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05189353, which also lists 1 linked publication.
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 1 Nov 2023.