Insulin Resistance in Multiple System Atrophy
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Homeostasis Model Assessment of insulin resistance (HOMA), MOntreal Cognitive Assessment (MoCA), Clinical characteristics of AMS patients, Brain Magnetic Resonance Imaging (MRI).
- Who it may be relevant to
- Registry conditions: Multiple System Atrophy. Basic parameters: from 30 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- 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
Primary outcome measures
- HOMA Index [Time frame: Day 0]
Secondary outcome measures (11)
- IRS-1pS312 (Insulin Receptor Substrate-1, Phosphorylated at Serine 312) concentration [Time frame: Day 0]
- Unified Multiple System Atrophy Rating Scale (UMSARS) score [Time frame: Day 0]
- Unified Multiple System Atrophy Rating Scale (UMSARS) score [Time frame: One year]
- COMPosite Autonomic Symptoms Score (COMPASS-31) [Time frame: Day 0]
- COMPosite Autonomic Symptoms Score (COMPASS-31) [Time frame: One year]
- AMS-Qol - Quality of life questionnaire [Time frame: Day 0]
- AMS-Qol - Quality of life questionnaire [Time frame: One year]
- MOntreal Cognitive Assessment (Moca) score [Time frame: Day 0]
- MOntreal Cognitive Assessment (Moca) score [Time frame: One year]
- Brain MRI volume [Time frame: Day 0]
- Brain MRI volume [Time frame: One year]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Health services research
Study locations
France · 1 center
- CHU de Bordeaux — Bordeaux
Identifiers
NCT: NCT04250493 · CHUBX 2018/30