Natural History and Disease Progression Biomarkers of Multiple System Atrophy (ASPIRE-MSA)
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|ClinicalTrials.gov Identifier: NCT04229173|
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : August 25, 2020
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
|Condition or disease||Intervention/treatment||Phase|
|Multiple System Atrophy||Diagnostic Test: MRI acquisition Diagnostic Test: DAT-SPECT Diagnostic Test: blood sample, cerebrospinal fluid (optional) Behavioral: Evaluations about motor abilities, depression, cognition and lifestyle Behavioral: Evaluation about depression cognition||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Natural History and Disease Progression Biomarkers of Multiple System Atrophy|
|Actual Study Start Date :||May 26, 2020|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||January 2021|
Patients with multiple system atrophy will be examined at baseline, 6 months and 12 months via the following procedures performed at all 3 visits:
Diagnostic Test: MRI acquisition
Diagnostic Test: DAT-SPECT
Imaging with DAT SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography)
Diagnostic Test: blood sample, cerebrospinal fluid (optional)
blood sample, cerebrospinal fluid
Behavioral: Evaluations about motor abilities, depression, cognition and lifestyle
Evaluations about motor abilities (UMSAR scale), depression (BDI scale), cognition (MoCA scale) and lifestyle (MSA- QoL)
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.
Diagnostic Test: MRI acquisition
Behavioral: Evaluation about depression cognition
Evaluations about depression (BDI scale), cognition (MoCA scale)
- 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)
- 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)
- 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)
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04229173
|Contact: OLIVIER RASCOL, MD, PHD||0033561779103 ext email@example.com|
|Contact: Wassilios MEISNER, MD, PHDfirstname.lastname@example.org|
|Toulouse, France, 31000|
|Contact: Rascol Olivier, PHD|
|Principal Investigator: Rascol olivier, PHD|
|Principal Investigator:||Olivier RASCOL, MD, PhD||University Hospital, Toulouse|