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Trial record 87 of 88 for:    "Brain Diseases" AND "Multiple System Atrophy"

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

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ClinicalTrials.gov Identifier: NCT02701036
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : June 29, 2017
Sponsor:
Collaborator:
German Center for Neurodegenerative Diseases (DZNE)
Information provided by (Responsible Party):
Prof. Dr. Thomas Klockgether, Ataxia Study Group

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.


Condition or disease
Late Onset Sporadic Cerebellar Ataxia

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.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 20 Years
Official Title: Sporadic Degenerative Ataxia With Adult Onset: Natural History Study (SPORTAX-NHS)
Study Start Date : April 2010
Estimated Primary Completion Date : December 2030
Estimated Study Completion Date : December 2030


Group/Cohort
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.
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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


  5. 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.

  6. 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

  7. 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 ]
    classified as "SAOA" can convert into MSAc, that is why they are followed with yearly clinical assessments.

  8. RBDSQ [ Time Frame: through study completion, an average of 10 years ]
    REM Behaviour Disorder Screening Questionnaire (RBDSQ)


Biospecimen Retention:   Samples With DNA
2x9 ml EDTA blood samples. Blood samples are taken according to established protocols for future genetic studies. The samples are sent to the Department of Medical Genetics (Tübingen, Germany).


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02701036


Contacts
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Contact: Ilaria Anna Giordano, MD 0049 228 287 15750 ilaria_anna.giordano@ukb.uni-bonn.de

Locations
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Austria
Department of Neurology, Medical University, Innsbruck Active, not recruiting
Innsbruck, Austria
Germany
Universitätsmedizin Berlin Charité Recruiting
Berlin, Germany
Contact: Sarah Doss, MD       sarah.doss@charite.de   
Department of Neurology, University of Bonn Recruiting
Bonn, Germany, 53105
Contact: Thomas Klockgether, Prof. Dr.       thomas.klockgether@ukb.uni-bonn.de   
Contact: Ilaria Giordano, MD       ilaria_anna.giordano@ukb.uni-bonn.de   
Department of Neurology, University Clinic Essen, University of Duisburg-Essen Recruiting
Essen, Germany
Contact: Dagmar Timmann, MD       dagmar.timmann-braun@uni-duisburg-essen.de   
Contact: Johanna Reinold       johanna.reinold@stud.uni-due.de   
Department of Neurology, University of Frankfurt Recruiting
Frankfurt, Germany
Contact: Jun-Suk Kang, MD       jun-suk.kang@med.uni-frankfurt.de   
Hamburg UKE Abt. Neuropädiatrie Active, not recruiting
Hamburg, Germany
Otto-von-Guericke Universität Magdeburg Recruiting
Magdeburg, Germany
Contact: Stefan Vielhaber, Prof. Dr.       stefan.vielhaber@med.ovgu.de   
Friedrich-Baur-Institut an der Neurologischen Klinik Recruiting
München, Germany
Contact: Thomas Klopstock, Prof. Dr.       thomas.klopstock@med.uni-muenchen.de   
Universitätsmedidzin Rostock - Klinik und Poliklinik für Neurologie Recruiting
Rostock, Germany
Contact: Cristoph Kamm, MD       christoph.kamm@med.uni-rostock.de   
Dept. of Neurodegenerative Diseases Tübingen Recruiting
Tübingen, Germany
Contact: Ludger Schoels, Prof. Dr.       ludger.schoels@dzne.de   
Italy
Department of Neuroscience, Federico II University Naples Recruiting
Naples, Italy
Contact: Alessandro Filla, MD       afilla@unina.it   
Contact: Antonella Antenora       antonella.antenora@virgilio.it   
Universita cattolica del sacro cuore Active, not recruiting
Rome, Italy
Netherlands
Radboud University Medical Center, Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour Active, not recruiting
Nijmegen, Netherlands
Norway
Oslo University Hospital Recruiting
Oslo, Norway
Contact: Chantal M.E. Tallaksen, MD, PhD       chantal.tallaksen@medisin.uio.no   
Sponsors and Collaborators
Ataxia Study Group
German Center for Neurodegenerative Diseases (DZNE)
Investigators
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Principal Investigator: Thomas Klockgether, MD Department of Neurology, Bonn, Germany

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Prof. Dr. Thomas Klockgether, Ataxia Study Group
ClinicalTrials.gov Identifier: NCT02701036     History of Changes
Other Study ID Numbers: SPORTAX 010/05
First Posted: March 8, 2016    Key Record Dates
Last Update Posted: June 29, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Prof. Dr. Thomas Klockgether, Ataxia Study Group:
sporadic ataxia
MSAc
SAOA
multiple system atrophy of cerebellar type
natural history

Additional relevant MeSH terms:
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Ataxia
Cerebellar Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases