- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04229173
Natural History and Disease Progression Biomarkers of Multiple System Atrophy (ASPIRE-MSA)
Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease characterised by a variable combination of parkinsonism, cerebellar impairment and autonomic dysfunction. The neuropathological hallmark is the accumulation of alpha-synuclein in oligodendrocytes. While some symptomatic treatments exist, neuroprotective treatments for MSA remain an urgent, unmet need. Moreover, at present there is not a single surrogate biomarker of MSA which could be used to inform clinical trials.
This study seeks to characterise the natural history of MSA on a panel of candidate biomarkers, pre-selected for being putative surrogates of the underlying neurodegenerative process
Study Overview
Status
Conditions
Detailed Description
Surrogate biomarkers are objectively measured characteristics of a disease which act as indicators of the underlying pathophysiological processes responsible for disease progression. Reduced grey matter volume in putamen, cerebellum and brainstem as measured with MRI have been consistently reported to differentiate MSA from other parkinsonian disorders. However, to date, there are no longitudinal studies examining the natural history of MSA on these structural neuroimaging markers over time. The magnitude of the abnormalities observed cross-sectionally in MSA compared to other parkinsonian disorders and the fast clinical progression of the disease make it very likely that structural changes can be observed even over short periods of time. There is also a strong scientific rationale for the potential of measures reflecting white matter integrity, cerebral iron deposition and presynaptic dopaminergic dysfunction, as well as levels of neurofilament light chain (NfL), alpha-synuclein and other proteins involved in the neurodegenerative process in MSA, to serve as progression biomarkers of the disease, although supporting evidence remains limited. A better understanding of the natural history of MSA over 6 and 12 months on a panel of candidate surrogate biomarkers is needed to better understand the disease, help optimise future trial designs in terms of patient selection, sample size and trial duration, and improve the ability to measure the therapeutic effects of novel treatments.
In evaluating potential progression markers of a neurodegenerative disease such as MSA, it is important to control for the normal effects of aging. Studies in healthy volunteers have shown regionally distinct effects of aging on both brain volume and dopamine transporter density, justifying the inclusion of healthy controls with a similar age and gender distribution than patients.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Bordeaux, France, 33076
- CHU de Bordeaux
-
Bron, France, 69677
- Hôpital Neurologique Pierre Wertheimer
-
Clermont Ferrand, France, 63003
- CHU Clermont Ferrand
-
Lille, France, 59037
- CHU Lille
-
Marseille, France, 13000
- Hopital De La Timone
-
Nancy, France, 54035
- Chu de Nancy
-
Nantes, France, 44093
- Clinique neurologique - Hôpital Laennec
-
Paris, France, 75013
- Hôpital Pitié-Salpétrière
-
Strasbourg, France, 67098
- Hopital de Hautepierre
-
Toulouse, France, 31000
- CHU
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
INCLUSION CRITERIA:
Applicable to MSA patients:
- Patients with possible or probable MSA according to consensus diagnosis criteria [Gilman et al., 2008]
- Patients aged between 30 and 80 years
- Patients at the early stages of the disease, defined as maximum 5 years since the onset of one of the following symptoms associated to MSA:
Parkinsonism Ataxia Orthostatic hypotension and/or urinary dysfunction - Patients with an anticipated survival of at least 3 years on the basis of Investigators' clinical judgment
Applicable to healthy controls:
- Participants with a similar age (+/- 5 years) and gender distribution compared to MSA patients
- Participants with absence of neurological pathology
- Patients aged between 25 and < 80 years
Applicable to both patients and healthy controls:
- Participants who voluntarily sign the written informed consent form, indicating that they understand the purpose of and procedures required for the study and are willing to participate in it Participants affiliated to the French social security health system
EXCLUSION CRITERIA:
Applicable to MSA patients:
- Speech impairment (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 1);
- Impairment in ambulation (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 7)
- Falling more frequently than once per week (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 8)
Applicable to both MSA patients and healthy controls:
- Participants with significant cognitive impairment (MoCA score <21)
- Any major medical or psychiatric condition which may compromise participation in the study or the safety, at the discretion of the Investigator
- Contraindications for MRI imaging, including claustrophobia and presence of metallic implants such as cardiac or auditory prostheses, pacemakers or cerebral clips
- Contraindications to obtain a FP-CIT SPECT(Single Photon Emission Computed Tomography) (i.e. known hypersensitivity to the active substance or to any of the excipients, or to iodine)
- Current pharmacological treatments that may alter the DAT(dopamine transporter ) SPECT (Single Photon Emission Computed Tomography) reading, including amphetamines, benzatropine, buproprion (amfebutamone), cocaine, mazindol, methylphenidate, phentermine or sertraline
- Females who are pregnant, breast feeding or of child bearing age without effective contraception
- Participants who lack the capacity to give informed consent
- Participants taking any investigational products within 3 months before baseline assessment
- Participant under adult autonomy protection system, legal guardianship or incapacitation.
Additional exclusion criteria concerning only patients consenting to the lumbar puncture:
- Coagulopathy and/or anticoagulant treatment
- Thrombocytopenia
- Intracranial hypertension
- Severe degenerative arthritis of the lumbar spine Patients failing to meet these criteria can still participate in the study and all other study assessments (with the exception of lumbar puncture) as appropriate.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: MSA patients
Patients with multiple system atrophy will be examined at baseline, 6 months and 12 months via the following procedures performed at all 3 visits:
|
MRI acquisition
Imaging with DAT SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography)
blood sample, cerebrospinal fluid
Evaluations about motor abilities (UMSAR scale), depression (BDI scale), cognition (MoCA scale) and lifestyle (MSA- QoL)
|
Other: Healthy volunteers
healthy.
Controls will undergo an MRI scan at baseline, 6 months and 12 months, and a DAT-SPECT(Dopamine Transporter, Single Photon Emission Computed Tomography) scan at baseline and 12 months.
|
MRI acquisition
Evaluations about depression (BDI scale), cognition (MoCA scale)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change putamen, cerebellum and brainstem volume measured on MRI
Time Frame: at 12 month
|
volume measured with T1-3D MRI, unit : Volume (mm3), Fer: R2* (s-1), diffusion: mean diffusivity (mm2s-1)
|
at 12 month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of disease progression on other measures of brain structural integrity and iron accumulation
Time Frame: 6 month and 12 month
|
volume measured with T1-3D MRI, unit : Volume (mm3), Fer: R2* (s-1), diffusion: mean diffusivity (mm2s-1)
|
6 month and 12 month
|
Effect of disease progression on the loss of presynaptic dopaminergic terminals in the striatum integrity and iron accumulation
Time Frame: 6 month and 12 month
|
volume measured with DAT SPECT (Single Photon Emission Computed Tomography), unit : binding potential (e.g ratio striatum/brain activity)
|
6 month and 12 month
|
Effect of disease progression on axonal damage as evidenced in biofluids
Time Frame: 6 month and 12 month
|
biomarkers dosages in blood and Cerebral Spinal Fluid total Concentration unit : pg/ml.
|
6 month and 12 month
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olivier RASCOL, MD, PhD, University Hospital, Toulouse
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Disease Attributes
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Pathological Conditions, Anatomical
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Hypotension
- Disease Progression
- Atrophy
- Multiple System Atrophy
- Shy-Drager Syndrome
Other Study ID Numbers
- RC31/19/0161
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple System Atrophy
-
Brigham and Women's HospitalBiohaven Pharmaceuticals, Inc.CompletedMultiple System Atrophy | Multiple System Atrophy, Parkinson Variant (Disorder) | Multiple System Atrophy, Cerebellar Variant | Multiple System Atrophy (MSA) With Orthostatic HypotensionUnited States
-
University of MichiganNational Institute of Neurological Disorders and Stroke (NINDS)CompletedMultiple System Atrophy - Parkinsonian Subtype (MSA-P) | Multiple System Atrophy - Cerebellar Subtype (MSA-C)United States
-
Dana HorakovaUnknownMultiple Sclerosis | Cognitive Change | Atrophy Brain | Atrophy; Spinal CordCzechia
-
Ono Pharmaceutical Co. LtdRecruitingMultiple System Atrophy (MSA)United States
-
Biohaven Pharmaceuticals, Inc.No longer availableMultiple System Atrophy (MSA)United States
-
University Hospital, BordeauxCompleted
-
AstraZenecaCompletedMultiple System Atrophy, MSAUnited States, Finland, Austria, France, Sweden, United Kingdom, Italy
-
Cytora Ltd.RecruitingMultiple System Atrophy | MSA - Multiple System AtrophyIsrael
-
Samsung Medical CenterUnknownMultiple System Atrophy, Cerebellar Variant (Disorder)Korea, Republic of
-
University of Texas Southwestern Medical CenterRecruiting
Clinical Trials on MRI acquisition
-
University Hospital, BordeauxGrant Agreement ERC SMHEARTNot yet recruiting
-
Johns Hopkins UniversityHyperfineCompletedExtracorporeal Membrane Oxygenation Complication | Acute Brain InjuryUnited States
-
University Hospital, BordeauxCompleted
-
University Hospital, GenevaRecruiting
-
Institut National de la Santé Et de la Recherche...CompletedParkinson's Disease | Multiple System AtrophyFrance
-
IHU StrasbourgCompleted
-
Assistance Publique Hopitaux De MarseilleUnknown
-
University Hospital, Clermont-FerrandRecruiting
-
Medical University of South CarolinaMUSC Center for Biomedical Research Excellence in Stroke RecoveryCompleted
-
CHU de ReimsUnknown