Natural History and Disease Progression Biomarkers of Multiple System Atrophy
Condition: Multiple System Atrophy
MeSH terms: Multiple System Atrophy; Shy-Drager Syndrome; Atrophy; Disease Progression
Study type: Interventional

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.
    

Intervention name(s): MRI acquisition; DAT-SPECT; blood sample, cerebrospinal fluid (optional); Evaluations about motor abilities, depression, cognition and lifestyle; Evaluation about depression cognition
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Behavioral; Behavioral
Intervention description(s): 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); Evaluations about depression (BDI scale), cognition (MoCA scale)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: MSA; MRI; Dat spect; Atrophy; Biomarkers