NCT04250493

Insulin Resistance in Multiple System Atrophy

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 124 (estimated)
• Sponsor: University Hospital, Bordeaux · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Accepted

Summary

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder. The pathologic hallmark is the accumulation of aggregated alpha-synuclein in oligodendrocytes forming glial cytoplasmic inclusions. Some symptomatic treatments are available while disease-modification remains an unmet treatment need. Post-mortem findings suggest insulin resistance, i.e. reduced insulin signaling, in the brains of MSA patients. The aim of this study is to complete the target validation of insulin resistance for future treatment trials.

Detailed description

Multiple system atrophy (MSA) patients have a poor prognosis with a median survival ranging between 6 and 10 years. MSA belongs to the synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein. We have recently shown brain insulin resistance (i.e. reduced insulin signaling) in post-mortem brain tissue of MSA patients and transgenic MSA mice, as illustrated by increased protein levels of insulin receptor substrate-1 phosphorylated at serine 312 (IRS-1pS312). Additionally, exendin-4, an approved anti-diabetic drug targeting glucagon-like peptide-1 (GLP-1) receptors, was capable of decreasing brain levels of IRS-1pS312 and preserving dopamine neurons in transgenic MSA mice. We further observed an inverse correlation between plasma neural-derived exosomal IRS-1pS312 levels and survival of dopamine neurons in transgenic MSA mice. The aim of this study is to further characterize peripheral and central insulin resistance in MSA patients, thereby validating this target for future treatment trials. For this purpose, fasting blood glucose and insulin levels will be determined in samples of MSA patients and healthy controls for a homeostatic model assessment of insulin resistance (HOMA). Additionally, IRS-1pS312 will be measured in neural-derived plasma exosomes of MSA patients and healthy controls.

Conditions

• Multiple System Atrophy

Interventions

Type	Name	Description
BIOLOGICAL	Homeostasis Model Assessment of insulin resistance (HOMA)	Fasting blood sample for : glucose, insulinemia, hemoglobin and lipid test to determine the Homeostasis Model Assessment of insulin resistance (HOMA) index
BEHAVIORAL	MOntreal Cognitive Assessment (MoCA)	Cognitive evaluation with MOntreal Cognitive Assessment (MoCA)
BEHAVIORAL	Clinical characteristics of AMS patients	Severity and progression of motor disorders assessed by the UMSARS scale, severity of dysautonomia assessed by the COMPASS31 scale ; quality of life questionnaire (AMS-Qol) for the level of difficulty experienced by the patient (on activities such as : move; walk; maintain balance; talk; feed)
PROCEDURE	Brain Magnetic Resonance Imaging (MRI)	Brain Magnetic Resonance Imaging (MRI) : putamen imaging, bridge and cerebellum; white substance hypersignals volume
BIOLOGICAL	Blood sampling	Optional blood sampling for the constitution of a biological collection

Timeline

• Start date: 2020-10-28
• Primary completion: 2026-10-28
• Completion: 2027-10-28
• First posted: 2020-01-31
• Last updated: 2025-07-20

Locations

1 site across 1 country: France