Investigation of the Relationship Between Peripheral and Central Metabolic Changes Induced by GLP-1 Agonists

NCT ID: NCT06818292

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-21
• Study Completion Date: 2024-12-06

Brief Summary

This study aims to investigate the acute effects of Liraglutide, a GLP-1 receptor agonist established in the treatment of type 2 diabetes and obesity, on brain metabolism, brain network function, and executive functioning as well as mood in healthy, normal-weight individuals. Given the emerging evidence of GLP-1's impact on brain function, including the modulation of reward processing and cognitive functions, this study will focus on the physiological changes induced by Liraglutide and their potential implications for brain health. The overall goal of this study is to assess how acute GLP-1 administration influences systemic and brain metabolism to modulate brain signalling and behaviour.

Detailed Description

Glucagon-like Peptide 1 (GLP-1) is a hormone secreted primarily by intestinal epithelial cells that plays a central role in promoting insulin secretion and reducing hunger and food intake. Liraglutide, a GLP-1 receptor agonist, has established benefits in regulating blood glucose and appetite and also directly acts on the brain through GLP-1 receptors. These receptors are widely distributed across brain regions, with high densities in the hypothalamus, brain stem, hippocampus, and in reward-related areas such as the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, the underlying effects of GLP-1 receptor activation on brain metabolism and functional brain networks remain poorly understood.

This study will address several key questions regarding the molecular, cellular, and cognitive changes that occur following the acute administration of Liraglutide. In particular, the investigation will focus on how GLP-1 administration modulates peripheral and central metabolism and on the influence of changes in brain metabolism on signaling. Furthermore, the relationship between brain metabolism, signaling, and psychological as well as cognitive outcomes will be examined.

Magnet resonance spectroscopy (MRS) will be used to measure changes in brain metabolism, with a focus on alterations in key metabolic pathways involved in neuronal function and energy homeostasis. In addition, biochemical profiles in blood will be examined to assess how peripheral metabolic changes may reflect or influence brain metabolism. Functional magnetic resonance imaging (fMRI) will also be employed to determine whether the observed alterations in brain metabolism correlate with changes in brain network connectivity and activity. Finally, correlations between these metabolic and connectivity changes and improvements in cognitive function and psychological parameters, such as executive function and mood (compared to placebo), will be evaluated.

The expected outcomes of this study are important insights into the neurobiological effects of Liraglutide and its potential to influence brain metabolism and functional dynamics. By elucidating the impact of GLP-1 analogues on brain metabolism and cognitive function, a better understanding of how metabolic regulation can affect brain signaling is anticipated. Given the prevalence of cognitive deficits in various psychiatric and neurological conditions, including obesity and type 2 diabetes, this research has the potential to contribute to the development of future therapeutic strategies involving GLP-1 receptor agonists.

Conditions

Healthy

Study Design

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

Study Groups

GLP-1 then Placebo

Participants will be randomly assigned to receive equivalent volumes of either Placebo (NaCl) or 0.6 mg of the pre-filled solutions from pen-injector Liraglutide (GLP-1 Agonist) in a randomized, counterbalanced order. The administration will occur at two time points: T1 and T3 with a washout period of at least 1 day between the two interventions to minimize carryover effects.

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: BIOLOGICAL

0.6 mg of the pre-filled solutions from pen-injector Liraglutide (GLP-1 Agonist)

Placebo

Intervention Type: BIOLOGICAL

0.1 mL NaCl

Placebo then GLP-1

Participants will be randomly assigned to receive equivalent volumes of either Placebo (NaCl) or 0.6 mg of the pre-filled solutions from pen-injector Liraglutide (GLP-1 Agonist) in a randomized, counterbalanced order. The administration will occur at two time points: T1 and T3 with a washout period of at least 1 day between the two interventions to minimize carryover effects.

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: BIOLOGICAL

0.6 mg of the pre-filled solutions from pen-injector Liraglutide (GLP-1 Agonist)

Placebo

Intervention Type: BIOLOGICAL

0.1 mL NaCl

Interventions

Liraglutide

0.6 mg of the pre-filled solutions from pen-injector Liraglutide (GLP-1 Agonist)

Intervention Type: BIOLOGICAL

Placebo

0.1 mL NaCl

Intervention Type: BIOLOGICAL

Other Intervention Names

GLP-1 Agonist

Eligibility Criteria

Inclusion Criteria

• Normal weight at study inclusion (BMI 18.5-25)
• Generally good physical condition without serious previous illnesses

Exclusion Criteria

• MRI contraindication: cardiac pacemakers, hearing aids, neurostimulation, insulin pumps, other potentially ferromagnetic implants, screws, clips, prostheses, metal splinters, etc., pregnancy, claustrophobia, extensive tattoos, medication that impairs thermoregulation
• Comorbidity: neurological or psychiatric conditions, cognitive impairments, chronic somatic disorders
• Intake of more than 40g of pure alcohol (for men) or more than 20g of pure alcohol (for women), smoking, regular drug use
• Pregnancy or nursing
• Current or within the past five years eating disorder, vegan diet or fasting within the past six months
• Regular medication intake
• Liraglutide contraindications: Hypersensitivity to liraglutide or other components of the medication, medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia endocrine neoplasia syndrome type 2 (MEN2) in personal or family history, history of pancreatitis, current pregnancy or breastfeeding, severe gastrointestinal motility disorders including gastroparesis, severe or terminal renal insufficiency

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 43 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Bonn

OTHER

Sponsor Role: collaborator

Johann Wolfgang Goethe University Hospital

OTHER

Sponsor Role: collaborator

Nils Opel

OTHER

Sponsor Role: lead

Responsible Party

Nils Opel

Prof Dr med

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sharmili Edwin Thanarajah, PD Dr med

Role: PRINCIPAL_INVESTIGATOR

Goethe University

Nils Gassen, Prof Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bonn

Locations

Department of Psychiatry and Psychotherapy, University Hospital Jena

Jena, Thuringia, Germany

Countries

Germany

Other Identifiers

2024-3513-BO

Identifier Type: -

Identifier Source: org_study_id