Multiple System AtrophyIRAMSNCT04250493
Insulin Resistance in Multiple System Atrophy
A study testing Homeostasis Model Assessment of insulin resistance (HOMA), MOntreal Cognitive Assessment (MoCA) and Clinical characteristics of AMS patients in people with Multiple System Atrophy, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple System Atrophy
- What is being tested?
- Homeostasis Model Assessment of insulin resistance (HOMA), MOntreal Cognitive Assessment (MoCA) and Clinical characteristics of AMS patients
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 1 siteFrance
- Study dates
- 28 Oct 2020to 28 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
Show all 10Show fewer
- Patients not suffering from a neurologic disorder
- Age > 30
- Written informed consent
- Patient covered by the national health system
Who cannot join
- 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
Show all 9Show fewer
- Pregnancy and breastfeeding
- MOCA ≤21
- Contraindication to perform an MRI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU de Bordeaux
Bordeaux, 33 076
Wassilios MEISSNER, 05 57 82 14 20, wassilios.meissner@chu-bordeaux.fr
About this study
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.
Read the 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
- Being tested
- Homeostasis Model Assessment of insulin resistance (HOMA), MOntreal Cognitive Assessment (MoCA), Clinical characteristics of AMS patients, Brain Magnetic Resonance Imaging (MRI), Blood sampling
- Keywords
- Multiple system atrophy, Neurodegenerative disease, Alpha synuclein, Insulin resistance
- Medical subject headings
- Multiple System Atrophy, Neurodegenerative Diseases, Parkinson Disease 4, Autosomal Dominant Lewy Body, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Homeostasis Model Assessment of insulin resistance (HOMA)Biological
Fasting blood sample for : glucose, insulinemia, hemoglobin and lipid test to determine the Homeostasis Model Assessment of insulin resistance (HOMA) index
MOntreal Cognitive Assessment (MoCA)Behavioural
Cognitive evaluation with MOntreal Cognitive Assessment (MoCA)
Clinical characteristics of AMS patientsBehavioural
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)
Brain Magnetic Resonance Imaging (MRI)Procedure or surgery
Brain Magnetic Resonance Imaging (MRI) : putamen imaging, bridge and cerebellum; white substance hypersignals volume
Blood samplingBiological
Optional blood sampling for the constitution of a biological collection
| Study group | Role | What they receive |
|---|---|---|
| MSA patient | Experimental | Patients will be recruited at the French Reference Center for MSA. Receives: Biological: Homeostasis Model Assessment of insulin resistance (HOMA); Behavioral: MOntreal Cognitive Assessment (MoCA); Behavioral: Clinical characteristics of AMS patients; Procedure: Brain Magnetic Resonance Imaging (MRI); Biological: Blood sampling |
| Control | Other | Healthy volunteer matched for age (+/- 5years) and sex with MSA patient. Receives: Biological: Homeostasis Model Assessment of insulin resistance (HOMA); Behavioral: MOntreal Cognitive Assessment (MoCA); Procedure: Brain Magnetic Resonance Imaging (MRI); Biological: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
HOMA Index
Homeostasis Model Assessment of insulin resistance (HOMA) index, calculated from a fasted blood glucose and insulin level between AMS patients and a formula-controlled group (insulinemia x glycemia)/22.5 insulinemia being expressed in mU/l and glucose in mmol/L.
Measured: Day 0
Secondary outcomes (11)
IRS-1pS312 (Insulin Receptor Substrate-1, Phosphorylated at Serine 312) concentration
Mean concentration of neuronal IRS-1pS312 in plasma exosomes
Measured: Day 0
Unified Multiple System Atrophy Rating Scale (UMSARS) score
UMSARS I (0=no disorder, 48=severe disorders): is an evaluation of activities of daily life via 12 items. It evaluates language, writing, autonomy (diet; dressing; hygiene), walking and the presence of possible urinary, sexual or intestinal disorders.
UMSARS II (0=no disorder, 56=severe disorders): consists of a motor examination on the basis of 14 items that allow to evaluate including facial expression, oculomotricity, oral expression, tremors or walking.
UMSARS III: consists of measurements of blood pressure and heart rate in the lying and standing position for 10 minutes every minute.
UMSARS IV : disability assessment from 1 to 5 (1= completely independent; 5 = totally dependent / dependent)
Measured: Day 0
Unified Multiple System Atrophy Rating Scale (UMSARS) score
UMSARS I (0=no disorder, 48=severe disorders): is an evaluation of activities of daily life via 12 items. It evaluates language, writing, autonomy (diet; dressing; hygiene), walking and the presence of possible urinary, sexual or intestinal disorders.
UMSARS II (0=no disorder, 56=severe disorders): consists of a motor examination on the basis of 14 items that allow to evaluate including facial expression, oculomotricity, oral expression, tremors or walking.
UMSARS III: consists of measurements of blood pressure and heart rate in the lying and standing position for 10 minutes every minute.
UMSARS IV : disability assessment from 1 to 5 (1= completely independent; 5 = totally dependent / dependent)
Measured: One year
COMPosite Autonomic Symptoms Score (COMPASS-31)
Assessment of dysautonomia. The scale consists of 31 items in 6 domains and provides an autonomic symptom score from 0 to 100. High values represent severe symptoms
Measured: Day 0
COMPosite Autonomic Symptoms Score (COMPASS-31)
Assessment of dysautonomia. The scale consists of 31 items in 6 domains and provides an autonomic symptom score from 0 to 100. High values represent severe symptoms
Measured: One year
AMS-Qol - Quality of life questionnaire
Quality of life questionnaire to collect the level of difficulty experienced by the patient (from no problem to extreme problem) during the 4 weeks preceding the interview on activities such as : move; walk; maintain balance; talk; feed. It also assesses how the patient feels about his disease
Measured: Day 0
AMS-Qol - Quality of life questionnaire
Quality of life questionnaire to collect the level of difficulty experienced by the patient (from no problem to extreme problem) during the 4 weeks preceding the interview on activities such as : move; walk; maintain balance; talk; feed. It also assesses how the patient feels about his disease
Measured: One year
MOntreal Cognitive Assessment (Moca) score
Moca evaluates short-term memory, visual spatial skills, executive functions, attention, concentration, working memory, language, abstraction abilities, computing and orientation in time and space. Cognitive impairment is assessed on the score of 30 points (27-30: no cognitive impairment; 21-26: mild)
Measured: Day 0
MOntreal Cognitive Assessment (Moca) score
Moca evaluates short-term memory, visual spatial skills, executive functions, attention, concentration, working memory, language, abstraction abilities, computing and orientation in time and space. Cognitive impairment is assessed on the score of 30 points (27-30: no cognitive impairment; 21-26: mild)
Measured: One year
Brain MRI volume
Imaging data (severity and progression of putamen atrophy, bridge and cerebellum in mm3; magnitude and progression of white substance hypersignals on T2-FLAIR images in mm3
Measured: Day 0
Brain MRI volume
Imaging data (severity and progression of putamen atrophy, bridge and cerebellum in mm3; magnitude and progression of white substance hypersignals on T2-FLAIR images in mm3
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2020
- Study start28 Oct 2020
- Primary completion28 Oct 2026 (estimated)
- Study completion28 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bordeaux, Labex Brain, Centre National de la Recherche Scientifique, France
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04250493
- Sponsor's protocol ID
- CHUBX 2018/30
- Acronym
- IRAMS
- Status last verified
- Jul 2025
- First submitted
- 29 Jan 2020
- Last updated
- 20 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin Resistance in Multiple System Atrophy
- ClinicalTrials.gov ID
- NCT04250493
- Acronym / sponsor ID
- IRAMS / CHUBX 2018/30
- Conditions
- Multiple System Atrophy
- Keywords
- Multiple system atrophy, Neurodegenerative disease, Alpha synuclein, Insulin resistance
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- University of Bordeaux, Labex Brain, Centre National de la Recherche Scientifique, France
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 28 Oct 2026 (estimated)
- Study completion
- 28 Oct 2027 (estimated)
- First posted
- 31 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSA patient | Experimental | Biological: Homeostasis Model Assessment of insulin resistance (HOMA), Behavioral: MOntreal Cognitive Assessment (MoCA), Behavioral: Clinical characteristics of AMS patients, Procedure: Brain Magnetic Resonance Imaging (MRI), Biological: Blood samplingPatients will be recruited at the French Reference Center for MSA. |
| Control | Other | Biological: Homeostasis Model Assessment of insulin resistance (HOMA), Behavioral: MOntreal Cognitive Assessment (MoCA), Procedure: Brain Magnetic Resonance Imaging (MRI), Biological: Blood samplingHealthy volunteer matched for age (+/- 5years) and sex with MSA patient. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- Patients not suffering from a neurologic disorder
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Biological | Control, MSA patient |
| MOntreal Cognitive Assessment (MoCA)Cognitive evaluation with MOntreal Cognitive Assessment (MoCA) | Behavioural | Control, MSA patient |
| Clinical characteristics of AMS patientsSeverity 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) | Behavioural | MSA patient |
| Brain Magnetic Resonance Imaging (MRI)Brain Magnetic Resonance Imaging (MRI) : putamen imaging, bridge and cerebellum; white substance hypersignals volume | Procedure or surgery | Control, MSA patient |
| Blood samplingOptional blood sampling for the constitution of a biological collection | Biological | Control, MSA patient |
Primary outcome
HOMA Index
Time frame: Day 0
Homeostasis Model Assessment of insulin resistance (HOMA) index, calculated from a fasted blood glucose and insulin level between AMS patients and a formula-controlled group (insulinemia x glycemia)/22.5 insulinemia being expressed in mU/l and glucose in mmol/L.
11 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Homeostasis Model Assessment of insulin resistance (HOMA), MOntreal Cognitive Assessment (MoCA) and Clinical characteristics of AMS patients in people with Multiple System Atrophy, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wassilios MEISSNER (05 57 82 14 20, wassilios.meissner@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HOMA Index (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2025.