Clinical trial NCT06818292: Investigation of the Relationship Between Peripheral and Central Metabolic Changes Induced by GLP-1 Agonists
Official title: Investigation of the Relationship Between Peripheral and Central Metabolic Changes Induced by GLP-1 Agonists
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: GLP-1
MR Spectroscopy
fMRI
Metabolism
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital, Bonn
name: Johann Wolfgang Goethe University Hospital
First posted: 2025-02-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Neuropsychology: Processing speed
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Neuropsychology: Attention
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Neuropsychology: Memory
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Neuropsychology: Verbal Fluency
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: MR spectroscopy
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Exploratory Proteomics of Autophagy Processes I
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Exploratory Proteomics of Autophagy Processes II
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
Secondary outcomes:
measure: Functional MRI
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Structural MR imaging
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Sleep
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Depression
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Anxiety
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Anhedonia
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Life quality
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Numeric Analog Scales
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Fatigue
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Metabolic processes
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Lipid profiling
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Transcription expression patterns
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Proteome/phosphoproteome/ubiquitinome patterns
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
measure: Exosomal protein patterns
timeFrame: Outcome measures are assessed during a one-week on-site visit per participant (placebo vs. liraglutide days) within an overall study period of 2 months
Other outcomes:
Locations:
city: Jena
country: Germany
facility: Department of Psychiatry and Psychotherapy, University Hospital Jena
state: Thuringia
Study officials:
affiliation: Goethe University
name: Sharmili Edwin Thanarajah, PD Dr med
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bonn
name: Nils Gassen, Prof Dr
role: PRINCIPAL_INVESTIGATOR
References: