NCT04229173

Natural History and Disease Progression Biomarkers of Multiple System Atrophy

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 61 (actual)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 30 Years – 80 Years
• Healthy volunteers: Accepted

Summary

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

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.

Conditions

• Multiple System Atrophy

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	MRI acquisition	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)
BEHAVIORAL	Evaluation about depression cognition	Evaluations about depression (BDI scale), cognition (MoCA scale)

Timeline

• Start date: 2020-05-26
• Primary completion: 2022-05-30
• Completion: 2022-10-28
• First posted: 2020-01-18
• Last updated: 2023-06-22

Locations

10 sites across 1 country: France