Ignite Creation Date:
2025-12-25 @ 1:27 AM
Ignite Modification Date:
2026-02-21 @ 3:22 AM
Study NCT ID:
NCT04250493
Status:
RECRUITING
Last Update Posted:
2025-07-20
First Post:
2020-01-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Insulin Resistance in Multiple System Atrophy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019578', 'term': 'Multiple System Atrophy'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'C565324', 'term': 'Parkinson Disease 4, Autosomal Dominant Lewy Body'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D054969', 'term': 'Primary Dysautonomias'}, {'id': 'D001342', 'term': 'Autonomic Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D000080874', 'term': 'Synucleinopathies'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000073216', 'term': 'Mental Status and Dementia Tests'}, {'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D009483', 'term': 'Neuropsychological Tests'}, {'id': 'D011581', 'term': 'Psychological Tests'}, {'id': 'D004191', 'term': 'Behavioral Disciplines and Activities'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'HEALTH_SERVICES_RESEARCH', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 124}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-10-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-10-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-18', 'studyFirstSubmitDate': '2020-01-29', 'studyFirstSubmitQcDate': '2020-01-29', 'lastUpdatePostDateStruct': {'date': '2025-07-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-01-31', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-10-28', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'HOMA Index', 'timeFrame': 'Day 0', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'IRS-1pS312 (Insulin Receptor Substrate-1, Phosphorylated at Serine 312) concentration', 'timeFrame': 'Day 0', 'description': 'Mean concentration of neuronal IRS-1pS312 in plasma exosomes'}, {'measure': 'Unified Multiple System Atrophy Rating Scale (UMSARS) score', 'timeFrame': 'Day 0', 'description': '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.\n\nUMSARS 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.\n\nUMSARS III: consists of measurements of blood pressure and heart rate in the lying and standing position for 10 minutes every minute.\n\nUMSARS IV : disability assessment from 1 to 5 (1= completely independent; 5 = totally dependent / dependent)'}, {'measure': 'Unified Multiple System Atrophy Rating Scale (UMSARS) score', 'timeFrame': 'One year', 'description': '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.\n\nUMSARS 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.\n\nUMSARS III: consists of measurements of blood pressure and heart rate in the lying and standing position for 10 minutes every minute.\n\nUMSARS IV : disability assessment from 1 to 5 (1= completely independent; 5 = totally dependent / dependent)'}, {'measure': 'COMPosite Autonomic Symptoms Score (COMPASS-31)', 'timeFrame': 'Day 0', 'description': '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'}, {'measure': 'COMPosite Autonomic Symptoms Score (COMPASS-31)', 'timeFrame': 'One year', 'description': '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'}, {'measure': 'AMS-Qol - Quality of life questionnaire', 'timeFrame': 'Day 0', 'description': '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'}, {'measure': 'AMS-Qol - Quality of life questionnaire', 'timeFrame': 'One year', 'description': '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'}, {'measure': 'MOntreal Cognitive Assessment (Moca) score', 'timeFrame': 'Day 0', 'description': '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)'}, {'measure': 'MOntreal Cognitive Assessment (Moca) score', 'timeFrame': 'One year', 'description': '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)'}, {'measure': 'Brain MRI volume', 'timeFrame': 'Day 0', 'description': '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'}, {'measure': 'Brain MRI volume', 'timeFrame': 'One year', 'description': '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'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Multiple system atrophy', 'Neurodegenerative disease', 'Alpha synuclein', 'Insulin resistance'], 'conditions': ['Multiple System Atrophy']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '30 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nPatients :\n\n* Patients suffering from "possible" or "probable" MSA according to clinical consensus criteria (Gilman et al., 2008).\n* Age \\> 30\n* Written informed consent\n* Patient covered by the national health system\n\nControls:\n\n* Patients not suffering from a neurologic disorder\n* Age \\> 30\n* Written informed consent\n* Patient covered by the national health system\n\nExclusion Criteria:\n\nFor patients and controls:\n\n* Presence of a diabetes\n* Treatment with corticosteroids, estrogen, atypical antipsychotics, and anti-retroviral agents\n* Patient under tutelage\n* Patient unable to give consent\n* Any other neurologic disorder\n* Pregnancy and breastfeeding\n* MOCA ≤21\n* Contraindication to perform an MRI'}, 'identificationModule': {'nctId': 'NCT04250493', 'acronym': 'IRAMS', 'briefTitle': 'Insulin Resistance in Multiple System Atrophy', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Bordeaux'}, 'officialTitle': 'Insulin Resistance in Multiple System Atrophy', 'orgStudyIdInfo': {'id': 'CHUBX 2018/30'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'MSA patient', 'description': 'Patients will be recruited at the French Reference Center for MSA.', 'interventionNames': ['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']}, {'type': 'OTHER', 'label': 'Control', 'description': 'Healthy volunteer matched for age (+/- 5years) and sex with MSA patient.', 'interventionNames': ['Biological: Homeostasis Model Assessment of insulin resistance (HOMA)', 'Behavioral: MOntreal Cognitive Assessment (MoCA)', 'Procedure: Brain Magnetic Resonance Imaging (MRI)', 'Biological: Blood sampling']}], 'interventions': [{'name': 'Homeostasis Model Assessment of insulin resistance (HOMA)', 'type': 'BIOLOGICAL', 'description': 'Fasting blood sample for : glucose, insulinemia, hemoglobin and lipid test to determine the Homeostasis Model Assessment of insulin resistance (HOMA) index', 'armGroupLabels': ['Control', 'MSA patient']}, {'name': 'MOntreal Cognitive Assessment (MoCA)', 'type': 'BEHAVIORAL', 'description': 'Cognitive evaluation with MOntreal Cognitive Assessment (MoCA)', 'armGroupLabels': ['Control', 'MSA patient']}, {'name': 'Clinical characteristics of AMS patients', 'type': 'BEHAVIORAL', 'description': '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)', 'armGroupLabels': ['MSA patient']}, {'name': 'Brain Magnetic Resonance Imaging (MRI)', 'type': 'PROCEDURE', 'description': 'Brain Magnetic Resonance Imaging (MRI) : putamen imaging, bridge and cerebellum; white substance hypersignals volume', 'armGroupLabels': ['Control', 'MSA patient']}, {'name': 'Blood sampling', 'type': 'BIOLOGICAL', 'description': 'Optional blood sampling for the constitution of a biological collection', 'armGroupLabels': ['Control', 'MSA patient']}]}, 'contactsLocationsModule': {'locations': [{'zip': '33 076', 'city': 'Bordeaux', 'status': 'RECRUITING', 'country': 'France', 'contacts': [{'name': 'Wassilios MEISSNER', 'role': 'CONTACT', 'email': 'wassilios.meissner@chu-bordeaux.fr', 'phone': '05 57 82 14 20'}], 'facility': 'CHU de Bordeaux', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}], 'centralContacts': [{'name': 'Wassilios MEISSNER', 'role': 'CONTACT', 'email': 'wassilios.meissner@chu-bordeaux.fr', 'phone': '05 57 82 14 20'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Bordeaux', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Bordeaux', 'class': 'OTHER'}, {'name': 'Labex Brain', 'class': 'OTHER'}, {'name': 'Centre National de la Recherche Scientifique, France', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}