Insulin Resistance in Multiple System Atrophy (IRAMS)

  • STATUS
    Recruiting
  • End date
    Oct 28, 2023
  • participants needed
    124
  • sponsor
    University Hospital, Bordeaux
Updated on 23 April 2022
insulin
insulin resistance
alpha-synuclein
Accepts healthy volunteers

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.

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.

Details
Condition Multiple System Atrophy
Treatment blood sampling, Montreal Cognitive Assessment (MoCA), Brain Magnetic Resonance Imaging (MRI), Homeostasis Model Assessment of insulin resistance (HOMA), Clinical characteristics of AMS patients
Clinical Study IdentifierNCT04250493
SponsorUniversity Hospital, Bordeaux
Last Modified on23 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients
Patients suffering from "possible" or "probable" MSA according to clinical consensus criteria (Gilman et al., 2008)
Age > 30
Written informed consent
Patient covered by the national health system
Controls
Patients not suffering from a neurologic disorder
Age > 30
Written informed consent
Patient covered by the national health system

Exclusion Criteria

For patients and controls
Presence of a diabetes
Treatment with corticosteroids, estrogen, atypical antipsychotics, and anti-retroviral agents
Patient under tutelage
Patient unable to give consent
Any other neurologic disorder
Pregnancy and breastfeeding
MOCA ≤21
Contraindication to perform an MRI
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