Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias

NCT04297891 | Unknown

• 2 other identifiers: SPAX-PBP441409627
• Study Type: observational
• Target: 250
• Locations: 7 countries
• Sites: 9

Brief Summary

The aim of this study is to determine the clinical spectrum and natural progression of Spastic Ataxias (SPAX) and related disorders in a prospective multicenter natural history study, identify digital, imaging and molecular biomarkers that can assist in diagnosis and therapy development and study the genetic etiology and molecular mechanisms of these diseases.

Conditions

Spastic Ataxia

Keywords

Spastic Ataxia; Biomarker; Genetic etiology; Molecular mechanisms; Natural History Study

Outcome Measures

Primary Outcomes (2)

• Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up

  Severity of the ataxia component of the disease will be assessed by application of the Scale for the Assessment and Rating of Ataxia (SARA). The total score is calculated as the sum of al items, yielding a total score between 0 and 38. Hereby, higher SARA scores indicate more severe disease.

  24 months

• Change of Spastic Paraplegia Rating Scale (SPRS) from baseline to 2-year follow-up

  Severity of the spasticity component of the disease will be assessed by application of the Spastic Paraplegia Rating Scale. The total score is calculated as the sum of al items, yielding a total score between 0 and 52. Hereby, higher SPRS scores indicate more severe disease.

  24 months

Secondary Outcomes (1)

• Change of Disease severity index - Autosomal recessive spastic ataxia of Charlevoix-Saguenay(DSI-ARSACS) from baseline to 2-year follow-up

  24 months

Other Outcomes (2)

• Change of the Patient-Reported Outcomes Measurement Information System (PROMIS) short form "physical function" 12a from baseline to 2-year follow-up

  24 months

• Change of the Patient-Reported Outcomes Measurement Information System (PROMIS) short form "social roles and activities" 8a from baseline to 2-year follow-up

  24 months

Study Arms (3)

ARSACS

Participants with genetically confirmed ARSACS (ORPHA:98) will be recruited. Target sample size for the ARSACS cohort is 120.

Other: Clinical rating scale to measure Ataxia disease severity and progression; Other: Clinical rating scale to measure spastic paraplegia disease severity and progression; Other: Disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS); Diagnostic Test: Next-Gen Sequencing (NGS)

SPG7

Participants with genetically confirmed SPG7 (ORPHA:99013) will be recruited. Target sample size for the SPG7 cohort is 72.

Other: Clinical rating scale to measure Ataxia disease severity and progression; Other: Clinical rating scale to measure spastic paraplegia disease severity and progression; Other: Disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS); Diagnostic Test: Next-Gen Sequencing (NGS)

Unrelated healthy control

Unrelated healthy controls Healthy controls may undergo the same study procedures as the ARSACS and SPG7 cohort. Target sample size for the control cohort is 50.

Other: Clinical rating scale to measure Ataxia disease severity and progression; Other: Clinical rating scale to measure spastic paraplegia disease severity and progression; Other: Disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS); Diagnostic Test: Next-Gen Sequencing (NGS)

Interventions

Clinical rating scale to measure Ataxia disease severity and progression OTHER

SARA is a clinical scale developed by Schmitz-Hübsch et al which assesses a range of different impairments in cerebellar ataxia. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test.

Also known as: Scale for the Assessment and rating of Ataxia (SARA)

ARSACS; SPG7; Unrelated healthy control

Clinical rating scale to measure spastic paraplegia disease severity and progression OTHER

A 13-item scale to rate functional impairment occurring in pure forms of spastic paraplegia (SP). Additional symptoms constituting a complicated form of SP are recorded in an inventory.

Also known as: Spastic Paraplegia Rating Scale (SPRS)

ARSACS; SPG7; Unrelated healthy control

Disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) OTHER

The DSI-ARSACS is a valid measure of disease severity for the adult ARSACS population that is able to distinguish between patients with different clinical profiles. It considers the 3 components (pyramidal, cerebellar, neuropathic) of the disease, and documents its content validity, internal consistency, and construct validity.

Also known as: DSI-ARSACS

ARSACS; SPG7; Unrelated healthy control

Next-Gen Sequencing (NGS) DIAGNOSTIC_TEST

Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics

ARSACS; SPG7; Unrelated healthy control

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Probands with clinically manifest and genetically confirmed spastic ataxia (genetic subtypes: ARSACS, SPG7) will be enrolled in this study. Additionally, healthy unrelated controls will be enrolled; these are necessary to contrast unspecific, gender- or age-related findings to disease specific findings.

You may qualify if:

• ARSACS cohort: genetic diagnosis of ARSACS and clinically manifest disease
• SPG7 cohort: genetic diagnosis of SPG7 and clinically manifest disease
• Unrelated healthy controls: no signs or history of neurological or psychiatric disease
• AND
• written informed consent provided
• AND
• Participants are willing and able to comply with study procedures

You may not qualify if:

• Missing informed consent
• For controls: evidence of a neurodegenerative disease or movement disorders; inability to give informed consent

Sponsors & Collaborators

• Dr. Rebecca Schule: lead
• German Center for Neurodegenerative Diseases (DZNE): collaborator
• German Research Foundation: collaborator

Study Sites (9)

Montreal Neurological Institute of McGill University, Department of Neurology and Neurosurgery and Human Genetics

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Université de Sherbrooke

Saguenay, Quebec, G7X 7X2, Canada

RECRUITING

Département d'information médicale (DIM); Département de Biostatistique, Santn 3emé Publique et Information Médicale (BIOSPIM)- Bâtiment Mazarie étage; Hôpitaux Universitaires Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

University Hospital Essen (AöR)

Essen, 45147, Germany

RECRUITING

IRCCS Fondazione Stella Maris

Pisa, 56128, Italy

RECRUITING

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

Nijmegen, 6525 GC, Netherlands

RECRUITING

Koç Univ. Hospital, KUTTAMNDAL

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

Department of Clinical Neurosciences, University of Cambridge; John Van Geest Cambridge Centre for Brain Repair

Cambridge, CB2 0PY, United Kingdom

RECRUITING

Related Publications (1)

• Hamdan A, Traschutz A, Beichert L, Chen X, Gagnon C, van de Warrenburg BP, Santorelli FM, Basak N, Coarelli G, Horvath R, Klebe S; PROSPAX consortium; EVIDENCE-RND consortium; Schule R, Hooker AC, Synofzik M, Karlsson MO. Integrated Modeling of Digital-Motor and Clinician-Reported Outcomes Using Item Response Theory: Towards Powerful Trials for Rare Neurological Diseases. CPT Pharmacometrics Syst Pharmacol. 2025 Nov;14(11):1857-1868. doi: 10.1002/psp4.70081. Epub 2025 Jul 21.

  PMID: 40685914 DERIVED

Related Links

• Website of the HSP Registry
• Website of the ARCA Registry

Biospecimen

Retention: SAMPLES WITH DNA

optional biosample collection including blood (DNA, serum, plasma, RNA, PBMC), urine, CSF, skin biopsy

MeSH Terms

Conditions

Spastic Ataxia

Interventions

Weights and Measures

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Rebecca Schüle, PD Dr.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

• Matthis Synofzik, Prof., Dr.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Schüle, PD Dr.

CONTACT

+49 7071 29; rebecca.schuele-freyer@uni-tuebingen.de

Matthis Synofzik, Prof., Dr.

CONTACT

+49 7071 29; matthis.synofzik@uni-tuebingen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Leading Consultant

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 6, 2020
• Study Start: September 1, 2020
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

DE (2); NL (1); CA (2); IT (1); TU (1); FR (1); GB (1)