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

NCT06818292 | Completed

• 1 other identifier: 2024-3513-BO
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

GLP-1; MR Spectroscopy; fMRI; Metabolism

Outcome Measures

Primary Outcomes (7)

• Neuropsychology: Processing speed

  Number Symbol Test, Letter-Number-Symbol Test, TMT-A. A composite score for processing speed will be derived from the Number Symbol Test, Letter-Number Symbol Test, and TMT-A. First, raw scores from each test will be normalized (e.g., converted into z-scores), taking into account that lower completion times on the TMT-A indicate better performance. The normalized scores will then be combined-after adjusting the direction of scores if necessary-by calculating their average to yield a single, unified measure of processing speed.

  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

• Neuropsychology: Attention

  TMT-B, D2-Test. A composite attention score will be created using the D2-Test and TMT-B. Raw scores from both tests will be standardized (e.g., as z-scores). For tests such as the TMT-B, if necessary, the scores will be adjusted (e.g., reverse-coded) so that higher values indicate better attention performance. The resulting standardized scores will be averaged to form a unified attention measure.

  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

• Neuropsychology: Memory

  VLMT-A, block span. A composite memory score will be computed from the VLM-T and Block Span test. Raw scores from each test will be standardized (e.g., into z-scores). These z-scores will then be averaged to yield a single measure of memory performance, reflecting both verbal and visuospatial working memory components.

  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

• Neuropsychology: Verbal Fluency

  MWT-B, Regensburg Word Fluency Test. A composite score for verbal fluency will be derived from the Regensburg Word Fluency Test and the MWT-B. First, raw scores for each test will be converted to standardized scores (e.g., z-scores). If needed, scores will be adjusted so that higher values consistently represent better performance. The standardized scores will then be averaged to create a single composite measure of verbal fluency.

  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

• MR spectroscopy

  metabolites between 0-4 ppm in the posterior cingulate cortex (PCC), medial cingulate cortex (MCC), and anterior insula

  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

• Exploratory Proteomics of Autophagy Processes I

  protein levels of autophagy biomarkers (e.g. LC3II \& p62) of isolated PBMCs (peripheral blood mononuclear cells) by Western Blotting

  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

• Exploratory Proteomics of Autophagy Processes II

  protein levels and protein phosphorylation by targeted and untargeted mass spectrometry-based proteomics and phosphoproteomics of isolated PBMCs (peripheral blood mononuclear cells)

  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 (14)

• Functional MRI

  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

• Structural MR imaging

  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

• Sleep

  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

• Depression

  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

• Anxiety

  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

Study Arms (2)

GLP-1 then Placebo

EXPERIMENTAL

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.

Biological: Liraglutide; Biological: Placebo

Placebo then GLP-1

EXPERIMENTAL

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.

Biological: Liraglutide; Biological: Placebo

Interventions

Liraglutide BIOLOGICAL

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

Also known as: GLP-1 Agonist

GLP-1 then Placebo; Placebo then GLP-1

Placebo BIOLOGICAL

0.1 mL NaCl

GLP-1 then Placebo; Placebo then GLP-1

Eligibility Criteria

• Age: 18 Years - 43 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Generally good physical condition without serious previous illnesses

You may not qualify if:

• 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

Sponsors & Collaborators

• Nils Opel: lead
• University Hospital, Bonn: collaborator
• Johann Wolfgang Goethe University Hospital: collaborator

Study Sites (1)

Department of Psychiatry and Psychotherapy, University Hospital Jena

Jena, Thuringia, 07743, Germany

Location

MeSH Terms

Interventions

Liraglutide

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Sharmili Edwin Thanarajah, PD Dr med

  Goethe University

  PRINCIPAL INVESTIGATOR

• Nils Gassen, Prof Dr

  University Hospital, Bonn

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof Dr med

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: February 10, 2025
• Study Start: October 21, 2024
• Primary Completion: December 6, 2024
• Study Completion: December 6, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

DE (1)