Clinical trial NCT02701036: Sporadic Degenerative Ataxia With Adult Onset: Natural History Study
Official title: Sporadic Degenerative Ataxia With Adult Onset: Natural History Study (SPORTAX-NHS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Late Onset Sporadic Cerebellar Ataxia
Keywords: sporadic ataxia
MSAc
SAOA
multiple system atrophy of cerebellar type
natural history
Lead sponsor: Ataxia Study Group
Sponsor class: OTHER
Collaborators: name: German Center for Neurodegenerative Diseases (DZNE)
First posted: 2016-03-08
Enrollment: 300
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of patients with adult onset degenerative ataxia, in which acquired and genetic causes of ataxia have been excluded.

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 description: 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.

Eligibility criteria: Inclusion Criteria:

* Progressive ataxia
* Disease onset after the age of 40 years
* Informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years, or, if not alive, age at death of more than 50 years, no consanguinity of parents)

Exclusion Criteria:

* No established acquired cause of ataxia

Clinical exclusion criteria:

* No onset of ataxia in association with stroke, encephalitis, sepsis, hyperthermia or heat stroke;
* no chronic diarrhea;
* no unexplained visual loss;
* no alcohol abuse;
* no chronic intake of anticonvulsant drugs;
* no other toxic causes; no malignancies;
* no rapid progression (development of severe ataxia in less than 12 weeks);
* no insulin-dependent diabetes mellitus

Imaging exclusion criteria:

* No evidence of multiple sclerosis, ischemia, hemorrhage or tumor of the posterior fossa;
* absence of signal abnormalities on T2/FLAIR-images except abnormalities compatible with MSA

Laboratory exclusion criteria:

* Negative molecular genetic testing for FRDA (only required if there is no cerebellar atrophy on MRI, SCA1, SCA2, SCA3, SCA6, FMR1 premutation (only required if prominent tremor, cognitive impairment and signal abnormality on T2/FLAIR images in the middle cerebellar peduncle);
* antineuronal antibodies negative (only required, if disease duration less than 3 years);
* normal levels of vitamin B12;
* VDRL negative;
* normal thyreoid function

Primary outcomes:
measure: Scale for the assessment and rating of ataxia (SARA)
timeFrame: through study completion, an average of 10 years
Secondary outcomes:
measure: Inventory of non-ataxia signs (INAS)
timeFrame: through study completion, an average of 10 years
measure: spinocerebellar ataxia functional index (SCAFI)
timeFrame: through study completion, an average of 10 years
measure: Unified Multiple System Atrophy Rating Scale (UMSARS)
timeFrame: through study completion, an average of 10 years
measure: Questionnaire for Cerebellar Multisystem Atrophy diagnostic criteria
timeFrame: through study completion, an average of 10 years
measure: EQ-5D
timeFrame: through study completion, an average of 10 years
measure: PHQ-9
timeFrame: through study completion, an average of 10 years
measure: Comparison of phenotype of cerebellar multiple system atrophy and sporadic adult onset ataxia of unknown etiology
timeFrame: through study completion, an average of 10 years
measure: RBDSQ
timeFrame: through study completion, an average of 10 years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Department of Neurology, Medical University, Innsbruck
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin Charité
city: Bonn
country: Germany
facility: Department of Neurology, University of Bonn
city: Essen
country: Germany
facility: Department of Neurology, University Clinic Essen, University of Duisburg-Essen
city: Frankfurt
country: Germany
facility: Department of Neurology, University of Frankfurt
city: Hamburg
country: Germany
facility: Hamburg UKE Abt. Neuropädiatrie
city: Magdeburg
country: Germany
facility: Otto-von-Guericke Universität Magdeburg
city: München
country: Germany
facility: Friedrich-Baur-Institut an der Neurologischen Klinik
city: Rostock
country: Germany
facility: Universitätsmedidzin Rostock - Klinik und Poliklinik für Neurologie
city: Tübingen
country: Germany
facility: Dept. of Neurodegenerative Diseases Tübingen
city: Naples
country: Italy
facility: Department of Neuroscience, Federico II University Naples
city: Rome
country: Italy
facility: Universita cattolica del sacro cuore
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center, Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Department of Neurology, Bonn, Germany
name: Thomas Klockgether, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giordano I, Harmuth F, Jacobi H, Paap B, Vielhaber S, Machts J, Schols L, Synofzik M, Sturm M, Tallaksen C, Wedding IM, Boesch S, Eigentler A, van de Warrenburg B, van Gaalen J, Kamm C, Dudesek A, Kang JS, Timmann D, Silvestri G, Masciullo M, Klopstock T, Neuhofer C, Ganos C, Filla A, Bauer P, Tezenas du Montcel S, Klockgether T. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. Neurology. 2017 Sep 5;89(10):1043-1049. doi: 10.1212/WNL.0000000000004311. Epub 2017 Aug 9.