The Importance of Ghrelin for Glucose Metabolism After Sleeve Gastrectomy

October 31, 2023 updated by: Marie-Louise Dichman, Hvidovre University Hospital
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
      • Hvidovre, Denmark, 2650
        • Hvidovre Universitets Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Pregnancy or breastfeeding.
  • Haemoglobin < 6,5 mM.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Gastric sleeve operated
12 subjects with normal glucose tolerance (NGT) operated with SG minimum 12 month earlier
Other: Placebo
Saline infusion
Other: Ghrelin
Ghrelin infusion
Placebo Comparator: Matched control group
12 weight-matched unoperated subjects with NGT
Other: Placebo
Saline infusion
Other: Ghrelin
Ghrelin infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
0-180 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Estimation of beta-cell function, calculated from insulin secretion rate using c-peptid and deconvolution from 0-10 min.
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)
When a steady state is reached at the end of the clamp, the glucose infusion rate represents insulin-mediated glucose uptake by the body.
160-180 minutes (the end of the clamp)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hvidovre University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institute of Biomedical Sciences, SUND, University of Copenhagen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 14, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 26, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 26, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 28, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-21037442

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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