Effect of GLP1 Receptor Agonist on Brain Insulin Responsiveness

March 25, 2025 updated by: University Hospital Tuebingen

Impact of the Incretin System on Brain Insulin Sensitivity in Humans with Normal Weight, Overweight and Obesity

The overarching goal of the current study is to investigate the effect of GLP-1 on brain insulin responsiveness in a randomized, single-blinded, within subject cross-over study design. To this end, investigators will compare the effect of the administration of semaglutide versus placebo, followed by an fMRI with administration of intranasal insulin or placebo.

Study Overview

Status

Status

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

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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

Investigate the effect of the GLP1 receptor agonist (i.e. 0.25 mg semaglutide) vs. placebo on the brain using functional magnetic resonance imaging (fMRI) in combination with 160IU intranasal insulin vs. placebo administration in healthy male and female participants of normal-weight and overweight/obesity. Participants will furthermore undergo tasks that assess cognitive functions and eating behavior. Brain insulin responsiveness (primary outcome) is defined as the cerebral response to intranasal insulin compared to placebo by means of cerebral blood flow and resting-state BOLD measurements. Secondary outcomes include diffusion weighted imaging, neural food cue reactivity, cognitive functions and metabolic predictors.

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 (Estimated)

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.
60

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 Locations

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • BMI between 18.5 and 24.9 kg/m2; and between 27.5 kg/m2 and 40 kg/m2
  • Written consent to participate in the study
  • Written consent to be informed about incidental findings

Exclusion Criteria:

  • Type 1 or type 2 diabetes, LADA, MODY, or cardiovascular diseases such as chronic heart failure, myocardial infarction, status post stroke
  • BMI < 18.5 or > 40 kg/m2
  • Persons who cannot legally give consent
  • Pregnancy or lactation
  • History of severe mental or somatic disorders including neurological diseases (incl. epileptic seizures)
  • Taking psychotropic drugs
  • Chronic diseases or medication that influence glucose metabolism
  • Regular use of analgesic drugs
  • Previous bariatric surgery
  • Known allergy against one or more of the used agents
  • Acute infection and/or antibiotic treatment within the last 4 weeks
  • Hemoglobin values less than 10.5 g/dl for women, less than 11.5 g/dl for men
  • Other diseases that in the opinion of the investigator may jeopardize the success of the study or indicate a risk to the volunteer
  • Participation in a lifestyle intervention study or a pharmaceutical study within the last 30 days
  • Metal implants which cannot be removed as pacemakers, artificial heart valve, electrical devices as insulin pumps, large tattoos, retainer over more than 4 teeth, contraceptive coil, implanted magnetic metal parts as screws or plates after a surgery
  • Persons with claustrophobia
  • Persons with tinnitus
  • Weight loss or gain of >5% in the last 3 months
  • Pancreatic diseases
  • History or family history of multiple endocrine neoplasia (MEN2) or medullary thyroid cancer
  • History of malignant thyroid disease
  • History of malignant disease in the past 5 years
  • Surgery in the last three months
  • Chronic tobacco use of more than 10 cigarettes/day
  • Women who do not consent to refrain from breastfeeding until 2 months after the end of the study
  • Women of childbearing age who do not consent to use safe method of contraception from 28 days before until 2 months after the end of the study or refrain from heterosexual intercourse during this time
  • Women of childbearing age who do not consent to take a pregnancy test

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: Crossover 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: GLP-1
Acute administration of 0.25 mg semaglutide (0.19 ml)
Other: Subcutaneous GLP1-RA
Subcutaneous administration of semaglutide
Placebo Comparator: Placebo
Acute administration of 0.19 ml NaCl
Other: Subcutaneous placebo
Subcutaneous administration of NaCl

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
Cerebral response after insulin compared to placebo nasal spray
Time Frame: 24 hours after semaglutide or placebo administration
Resting-state cerebral blood flow and BOLD-fMRI response from before to 30 min after nasal spray administration
24 hours after semaglutide or placebo administration

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
Neural food-cue reactivity after insulin compared to placebo nasal spray
Time Frame: 24 hours after semaglutide or placebo administration
BOLD-fMRI response to food cues 30 min after nasal spray administration
24 hours after semaglutide or placebo administration
Diffusion-weighted imaging (DWI)
Time Frame: 24 hours after semaglutide or placebo administration
Diffusion weighted parameter based on MRI measurements
24 hours after semaglutide or placebo administration
Heart rate variability (HRV)
Time Frame: 24 hours after semaglutide or placebo administration
HRV based on ECG measurements
24 hours after semaglutide or placebo administration
Change in subjective feeling of hunger and food craving
Time Frame: 24 hours after semaglutide or placebo administration
On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using questionnaires.
24 hours after semaglutide or placebo administration
Change in mood
Time Frame: 24 hours after semaglutide or placebo administration
Using a questionnaire, positive and negative affect state will be assessed.
24 hours after semaglutide or placebo administration
Performance during cognitive tests
Time Frame: 24 hours after semaglutide or placebo administration
Cambridge Cognition Tests Battery
24 hours after semaglutide or placebo administration

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.
University Hospital Tuebingen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Andreas L. Birkenfeld, MD, Institute for Diabetes research and Metabolic Diseases at the University of Tubingen

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.
July 1, 2024

Primary Completion (Estimated)

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.
July 31, 2027

Study Completion (Estimated)

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.
December 31, 2027

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).
June 27, 2024

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.
June 27, 2024

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.
July 5, 2024

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.
March 30, 2025

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.
March 25, 2025

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.
June 1, 2024

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.
  • 065/2024BO1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings