Clinical Trial: Sporadic Degenerative Ataxia With Adult Onset: Natural History Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Sporadic Degenerative Ataxia With Adult Onset: Natural History Study (SPORTAX-NHS)

Brief Summary:

The key goals of SPORTAX-NHS is to compare the phenotype of multiple system atrophy of cerebellar type (MSA-C) and sporadic adult onset ataxia of unknown aetiology (SAOA) and to determine the rate of disease progression in both groups including determination of the factors that predict the development of MSA-C vs. SAOA, and at which time after onset of ataxia, a reliable distinction between both disorders is possible.

The planned study will also allow to collect blood samples and other biomaterials from patients with sporadic ataxia, which will be useful for future genetic and biomarker studies.


Detailed Summary:

Progressive ataxia frequently starts in adults without a familial background. These patients may suffer from an acquired ataxia or a genetically determined ataxia despite negative family history. In the majority of them, however, a genetic or acquired cause of ataxia cannot be identified suggesting a sporadic degenerative ataxia. They can be subdivided into two groups. In one group, the underlying brain disease is multiple system atrophy (MSA), specifically MSA of cerebellar type (MSA-C). The characteristic clinical feature of MSA is the presence of severe autonomic failure defined by orthostatic hypotension or urinary incontinence. The second group is distinguished from MSA-C by the lasting absence of severe autonomic failure. These patients have been designated as sporadic adult onset ataxia of unknown aetiology (SAOA). In the first years after ataxia onset, a distinction between MSA-C and SAOA is often not possible.

There are only few studies comparing the phenotype of MSA-C and SAOA, and longitudinal studies focussing on the evolution of the phenotype of these disorders are completely lacking. In particular, the progression rate of SAOA compared to MSA-C has not been defined. In addition, it is unknown which factors predict the development of MSA-C vs. SAOA, and at which time after onset of ataxia, a reliable distinction between both disorders is possible.

To answer these questions, we plan to create a European registry of patients with sporadic degenerative ataxia of adult onset and to perform a natural history study. The planned study will also allow to collect blood samples and other biomaterials from patients with sporadic ataxia, which will be useful for future genetic and biomarker studies.


Sponsor: Ataxia Study Group

Current Primary Outcome:

  • Scale for the assessment and rating of ataxia (SARA) [ Time Frame: through study completion, an average of 10 years ]
    Both conditions (SAOA and MSAc) are part of neurodegenerative diseases, chronic progressive disorders. Their disease progression, can be measured using a validated ataxia scale, SARA. SARA was evaluated in two large validation trials performed by the EUROSCA clinical group and was found to be easy to use, reliable, and valid.
  • Comparison of phenotype of cerebellar multiple system atrophy and sporadic adult onset ataxia of unknown etiology [ Time Frame: through study completion, an average of 10 years ]
    A comparison between phenotype of multiple system atrophy of cerebellar type (MSA-C) and sporadic adult onset ataxia of unknown etiology (SAOA) and calculation of rate of their disease progression will be done. Patient that at the beginning are classified as "SAOA" can convert into MSAc, that is why they are followed with yearly clinical assessments.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Inventory of non-ataxia signs (INAS) [ Time Frame: through study completion, an average of 10 years ]
    The occurrence of accompanying non-ataxia symptoms is recorded using INAS.
  • spinocerebellar ataxia functional index (SCAFI) [ Time Frame: through study completion, an average of 10 years ]
    to assess the severity of ataxia in an objective way, three quantitative tests, 8m-walk, 9HPT (hole peg test) and PATA rate (timed speech task) are used.
  • Unified Multiple System Atrophy Rating Scale (UMSARS) [ Time Frame: through study completion, an average of 10 years ]
    UMSARS is a validated scale for multiple system atrophy used to assess additional symptoms typically occurring in MSA. The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale.
  • Questionnaire for Cerebellar Multisystem Atrophy diagnostic criteria [ Time Frame: through study completion, an average of 10 years ]

    To distinguish between SAOA and MSAc adjusted criteria for multiple system atrophy of cerebellar type on the basis of consensus statement on the diagnostic criteria for MSAc are used (Second consensus statement on the diagnosis of multiple system atrophy: Neurology. 2008 Aug 26; 71(9): 670-676).

    Probable MSAc requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and cerebellar ataxia. Possible cerebellar MSA requires a sporadic, progressive adult-onset disease including cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality (Babinski sign with hyperreflexia, Stridor, Parkinsonism (bradykinesia and rigidity), Atrophy on MRI of putamen, middle cerebellar peduncle, or pons, Hypometabolism on FDG-PET in putamen, Presynaptic nigrostriatal dopaminergic denervation on SPECT or PET. If both criteria are not met patient is classified as a SAOA.

  • EQ-5D [ Time Frame: through study completion, an average of 10 years ]
    Health related Quality of life is assessed using EQ-5D, a generic instrument that has been developed and validated by the EuroQuol Group (1990) and is available in validated translations for use as a questionnaire.
  • PHQ-9 [ Time Frame: through study completion, an average of 10 years ]
    Assessment of depressive symptoms is done using a validated 9-item short form of the Patient Health Questionnaire (PHQ), a questionnaire that has been developed to screen for psychiatric co-morbidity in unselected populations


Original Secondary Outcome: Same as current

Information By: Ataxia Study Group

Dates:
Date Received: January 28, 2016
Date Started: April 2010
Date Completion: December 2030
Last Updated: March 9, 2016
Last Verified: March 2016