Sporadic Degenerative Ataxia With Adult Onset: Natural History Study

NCT ID: NCT02701036

Last Updated: 2017-06-29

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2030-12-31

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.

Conditions

Late Onset Sporadic Cerebellar Ataxia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

sporadic adult onset ataxia

SAOA denotes the non-hereditary degenerative adult-onset ataxia disorders that are distinct from multiple system atrophy (MSA). SAOA is a group of ataxia of unknown etiology characterized by a slowly progressive cerebellar syndrome starting around the age of 50 years. Possibly is accompanied by signs of mild autonomic dysfunction that do not meet the criteria of severe autonomic failure required for a diagnosis of MSA.

No interventions assigned to this group

cerebellar multiple system atrophy

Multiple system atrophy of cerebellar type is a cerebellar syndrome with sporadic onset developing in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, orthostatic hypotension and atrophy of the cerebellum, brainstem, and middle cerebellar peduncles.

No interventions assigned to this group

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

• 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

• 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

• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

German Center for Neurodegenerative Diseases (DZNE)

OTHER

Sponsor Role: collaborator

Ataxia Study Group

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Thomas Klockgether

Prof. Dr. Thomas Klockgether

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Klockgether, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Bonn, Germany

Locations

Department of Neurology, Medical University, Innsbruck

Innsbruck, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Universitätsmedizin Berlin Charité

Berlin, , Germany

Site Status: RECRUITING

Department of Neurology, University of Bonn

Bonn, , Germany

Site Status: RECRUITING

Department of Neurology, University Clinic Essen, University of Duisburg-Essen

Essen, , Germany

Site Status: RECRUITING

Department of Neurology, University of Frankfurt

Frankfurt, , Germany

Site Status: RECRUITING

Hamburg UKE Abt. Neuropädiatrie

Hamburg, , Germany

Site Status: ACTIVE_NOT_RECRUITING

Otto-von-Guericke Universität Magdeburg

Magdeburg, , Germany

Site Status: RECRUITING

Friedrich-Baur-Institut an der Neurologischen Klinik

München, , Germany

Site Status: RECRUITING

Universitätsmedidzin Rostock - Klinik und Poliklinik für Neurologie

Rostock, , Germany

Site Status: RECRUITING

Dept. of Neurodegenerative Diseases Tübingen

Tübingen, , Germany

Site Status: RECRUITING

Department of Neuroscience, Federico II University Naples

Naples, , Italy

Site Status: RECRUITING

Universita cattolica del sacro cuore

Rome, , Italy

Site Status: ACTIVE_NOT_RECRUITING

Radboud University Medical Center, Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour

Nijmegen, , Netherlands

Site Status: ACTIVE_NOT_RECRUITING

Oslo University Hospital

Oslo, , Norway

Site Status: RECRUITING

Countries

Austria; Germany; Italy; Netherlands; Norway

Central Contacts

Ilaria Anna Giordano, MD

Role: CONTACT

ilaria_anna.giordano@ukb.uni-bonn.de

0049 228 287 15750

Facility Contacts

Sarah Doss, MD

Role: primary

sarah.doss@charite.de

Thomas Klockgether, Prof. Dr.

Role: primary

thomas.klockgether@ukb.uni-bonn.de

Ilaria Giordano, MD

Role: backup

ilaria_anna.giordano@ukb.uni-bonn.de

Dagmar Timmann, MD

Role: primary

dagmar.timmann-braun@uni-duisburg-essen.de

Johanna Reinold

Role: backup

johanna.reinold@stud.uni-due.de

Jun-Suk Kang, MD

Role: primary

jun-suk.kang@med.uni-frankfurt.de

Stefan Vielhaber, Prof. Dr.

Role: primary

stefan.vielhaber@med.ovgu.de

Thomas Klopstock, Prof. Dr.

Role: primary

thomas.klopstock@med.uni-muenchen.de

Cristoph Kamm, MD

Role: primary

christoph.kamm@med.uni-rostock.de

Ludger Schoels, Prof. Dr.

Role: primary

ludger.schoels@dzne.de

Alessandro Filla, MD

Role: primary

afilla@unina.it

Antonella Antenora

Role: backup

antonella.antenora@virgilio.it

Chantal M.E. Tallaksen, MD, PhD

Role: primary

chantal.tallaksen@medisin.uio.no

References

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.

Reference Type: DERIVED

PMID: 28794257 (View on PubMed)

Related Links

http://www.ataxia-study-group.net/html/studies/sportax

Sportax Database

Other Identifiers

SPORTAX 010/05

Identifier Type: -

Identifier Source: org_study_id