Sporadic Degenerative Ataxia With Adult Onset: Natural History Study

Официальное название

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

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Scale for the assessment and rating of ataxia (SARA) [Срок оценки: through study completion, an average of 10 years]

Вторичные конечные точки (8)

• Inventory of non-ataxia signs (INAS) [Срок оценки: through study completion, an average of 10 years]
• spinocerebellar ataxia functional index (SCAFI) [Срок оценки: through study completion, an average of 10 years]
• Unified Multiple System Atrophy Rating Scale (UMSARS) [Срок оценки: through study completion, an average of 10 years]
• Questionnaire for Cerebellar Multisystem Atrophy diagnostic criteria [Срок оценки: through study completion, an average of 10 years]
• EQ-5D [Срок оценки: through study completion, an average of 10 years]
• PHQ-9 [Срок оценки: through study completion, an average of 10 years]
• Comparison of phenotype of cerebellar multiple system atrophy and sporadic adult onset ataxia of unknown etiology [Срок оценки: through study completion, an average of 10 years]
• RBDSQ [Срок оценки: through study completion, an average of 10 years]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 9 центров

• Universitätsmedizin Berlin Charité — Berlin
• Department of Neurology, University of Bonn — Bonn
• Department of Neurology, University Clinic Essen, University of Duisburg-Essen — Essen
• Department of Neurology, University of Frankfurt — Frankfurt
• Hamburg UKE Abt. Neuropädiatrie — Hamburg
• Otto-von-Guericke Universität Magdeburg — Magdeburg
• Friedrich-Baur-Institut an der Neurologischen Klinik — München
• Universitätsmedidzin Rostock - Klinik und Poliklinik für Neurologie — Rostock
• … и ещё 1 центр

Италия · 2 центра

• Department of Neuroscience, Federico II University Naples — Naples
• Universita cattolica del sacro cuore — Rome

Австрия · 1 центр

• Department of Neurology, Medical University, Innsbruck — Innsbruck

Нидерланды · 1 центр

• Radboud University Medical Center, Department of Neurology, Donders Institute for Brain, C — Nijmegen

Норвегия · 1 центр

• Oslo University Hospital — Oslo

Публикации

• 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 degener PMID 28794257

Идентификаторы

NCT: NCT02701036 · SPORTAX 010/05

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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