Effect of GLP1 Receptor Agonist on Brain Insulin Responsiveness

NCT ID: NCT06487832

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2027-12-31

Brief Summary

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.

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.

Conditions

Normal Weight; Overweight and Obesity; Insulin Sensitivity; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

GLP-1

Acute administration of 0.25 mg semaglutide (0.19 ml)

Group Type: EXPERIMENTAL

Subcutaneous GLP1-RA

Intervention Type: OTHER

Subcutaneous administration of semaglutide

Placebo

Acute administration of 0.19 ml NaCl

Group Type: PLACEBO_COMPARATOR

Subcutaneous placebo

Intervention Type: OTHER

Subcutaneous administration of NaCl

Interventions

Subcutaneous GLP1-RA

Subcutaneous administration of semaglutide

Intervention Type: OTHER

Subcutaneous placebo

Subcutaneous administration of NaCl

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas L. Birkenfeld, MD

Role: STUDY_DIRECTOR

Institute for Diabetes research and Metabolic Diseases at the University of Tubingen

Locations

University Clinic Tubingen, Department of Internal Medicine IV

Tübingen, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Stephanie Kullmann, PhD

Role: CONTACT

stephanie.kullmann@med.uni-tuebingen.de

0049707129 ext. 87703

Facility Contacts

Stephanie Kullmann, PhD

Role: primary

stephanie.kullmann@med.uni-tuebingen.de

0049707129 ext. 87703

Other Identifiers

065/2024BO1

Identifier Type: -

Identifier Source: org_study_id