Ataxias, hereditary spastic paraplegias (HSP), and spastic ataxias (collectively referred to as SPAX diseases) are rare neurological conditions that cause progressive problems with walking, balance, coordination, and daily activities. Although many SPAX diseases are caused by specific genetic changes, there is still limited knowledge about how symptoms develop over time, how fast the diseases progress, and which clinical or biological measures best reflect meaningful changes for patients. The TreatHSP Master Protocol establishes an adaptive natural history study platform designed to improve the understanding of SPAX diseases across all ages and disease stages. Within this platform, the TreatHSP/SPAX study serves as the core natural history study, providing a shared framework for long-term clinical follow-up, standardized outcome assessments, and biosample collection. Participants enrolled in TreatHSP/SPAX are followed over time to document disease progression using clinical examinations, patient- and caregiver-reported outcomes, digital movement measures, imaging, and biological samples. In addition to this core dataset, the TreatHSP Platform allows optional, disease- or hypothesis-specific substudies to be added over time in selected participant groups. These additional assessments are introduced under the same master protocol, without creating separate stand-alone studies. The overall goal of the TreatHSP Master Protocol is to generate high-quality natural history data, identify sensitive and patient-relevant outcome measures, and support the development of future therapies for ataxias, hereditary spastic paraplegias, and spastic ataxias.
Overview and Objectives: The TreatHSP Protocol defines an adaptive observational study platform for natural history research, outcome development, and biomarker discovery in ataxias, hereditary spastic paraplegias (HSP), and spastic ataxias (SPAX diseases). The platform is designed to support longitudinal, regulatory-grade data collection across genetically and clinically heterogeneous rare neurological disorders. Within the TreatHSP platform, TreatHSP/SPAX represents the core natural history study. All participants are enrolled into TreatHSP/SPAX and undergo a standardized set of core assessments, forming the backbone of the platform. Additional disease- or hypothesis-specific investigations may be conducted within the same platform framework. The primary objectives of the TreatHSP platform are to: Characterize the longitudinal clinical course of SPAX diseases across genotypes, ages, and disease stages. Identify, develop, and validate patient-relevant clinical outcome assessments. Discover and validate molecular, imaging, digital, and functional biomarkers relevant for disease progression, prognosis, and therapy development. Establish a harmonized data and biosample resource to support clinical trial readiness and secondary research. Adaptive Platform Design: The TreatHSP Master Protocol follows design principles analogous to interventional platform trials, adapted for observational research. A single master protocol governs all study activities, including governance, ethics, consent, data protection, and quality assurance. The TreatHSP/SPAX core natural history study defines: Core eligibility principles Mandatory clinical, functional, and patient-reported assessments Standardized biosample collection Common data elements and anchor outcome measures Within this framework, additional adaptive Natural History Study appendices may be introduced as protocol amendments. These appendices add optional assessments (e.g. digital mobility monitoring, advanced imaging, biomarker studies) in predefined participant subsets, while preserving the integrity of the core cohort and dataset. This adaptive design enables parallel investigation of multiple disease subgroups and research questions under a single, continuously evolving protocol. Study Population: The platform includes: Individuals of all ages with a clinical or genetic diagnosis of an ataxia, hereditary spastic paraplegia, or spastic ataxia, including presymptomatic mutation carriers. Selected affected or unaffected family members. Healthy unrelated control participants for selected analyses. Registry Procedures and Quality Assurance: The TreatHSP/SPAX core study functions as a structured patient registry within the TreatHSP Platform and follows predefined quality standards. Data Collection and Validation: Data are collected using standardized electronic case report forms. Automated data checks are applied to ensure validity, plausibility, and internal consistency. Queries are generated and resolved by trained study personnel. Source Data Verification: Data entered into the registry may be verified against source documents (e.g. medical records, imaging reports, laboratory data) using a risk-based and sample-based approach. Data Dictionary: A comprehensive data dictionary defines all variables collected within the platform, including variable definitions, data sources, coding standards (e.g. Human Phenotype Ontology, MedDRA where applicable), and reference ranges when relevant. Standard Operating Procedures: Standard Operating Procedures govern patient recruitment, informed consent, data collection, data management, biosample handling, quality control, statistical analysis, reporting, and change management for adaptive protocol amendments. Monitoring and Auditing: Central data monitoring and periodic site-level reviews are conducted to ensure data quality, protocol adherence, and compliance with ethical and regulatory requirements. Sample Size and Statistical Considerations: Due to the rarity and heterogeneity of SPAX diseases, the TreatHSP Platform does not define a fixed sample size. Enrollment is open-ended to ensure broad representation across disease subtypes. Statistical analyses are primarily longitudinal and descriptive, with detailed analysis plans defined for specific substudies as needed. Handling of Missing Data: Missing data are explicitly documented and categorized. Statistical analyses account for missing data using appropriate longitudinal methods and sensitivity analyses, depending on the research question. Data Protection and Governance: All data are pseudonymized and handled in accordance with applicable data protection regulations. Access to identifiable information is restricted to authorized personnel. Data sharing for secondary research is governed by defined access procedures and ethical approvals.
Study Type
OBSERVATIONAL
Enrollment
4,000
Medical University Innsbruck, Department of Neurology
Innsbruck, Austria
RECRUITINGCentre of Hereditary Ataxias, Department of Neurology and Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol and Homolka University Hospital
Prague, Czechia
RECRUITINGParis Brain Institute ICM CRMR Neurogénétique, Hôpital de la Pitié-Salpêtrière Sorbonne Université UM75 Inserm U1127 CNRS UMR 7225 47 boulevard de l'Hôpital, CS21414
Paris, France
RECRUITINGRuhr University Bochum, Institute for Neuroinformatics (INI)
Modified Spastic Paraplegia Rating Scale
The modified Spastic Paraplegia Rating Scale (mSPRS) is a clinician-reported outcome measure assessing disease severity in hereditary spastic paraplegia and related spastic movement disorders. It evaluates functional mobility, spasticity, muscle strength, pain and bladder function. The mSPRS is adapted from the original Spastic Paraplegia Rating Scale to improve feasibility and sensitivity to change in longitudinal studies. It can be applied in individuals aged 5 years and older, with higher scores indicating greater disease severity. The mSPRS serves as the primary outcome measure for the assessment of disease severity in all participants with hereditary spastic paraplegia.
Time frame: Through study completion, an average of 5 years, measured annually
Scale for the Assessment and Rating of Ataxia (SARA)
The Scale for the Assessment and Rating of Ataxia (SARA) is a standardized clinician-reported outcome measure used to quantify the severity of ataxia. It assesses key domains including gait, stance, sitting, speech disturbance, limb coordination, and fine motor control. The SARA provides a global measure of ataxia-related motor impairment and is widely used in both clinical practice and longitudinal research studies. The SARA is applied in study participants aged 8 years and older, with higher scores indicating greater ataxia severity. The SARA serves as the primary outcome measure for the assessment of disease severity in all participants with ataxia.
Time frame: Through study completion, an average of 5 years, measured annually
SPAX Composite Scale (SPAXCOM)
SPAXCOM is a clinician-reported composite outcome measure developed to assess disease severity in individuals with spastic ataxia. It integrates key motor and functional domains relevant to spastic-ataxic phenotypes, including gait and balance, coordination, spasticity, and functional mobility. SPAXCOM is designed to capture the combined contribution of pyramidal and cerebellar dysfunction and to provide a sensitive measure of disease severity and progression in spastic ataxia. Higher scores indicate greater disease severity. SPAXCOM serves as the primary outcome measure for participants with spastic ataxia.
Time frame: Through study completion, an average of 5 years, measured annually
Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL)
The Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) assesses the impact of neurological impairment on everyday functioning, including walking, balance, speech, hand function, and self-care. In this study, both a clinician-reported (ClinRO) version and a patient-reported (PROM) version of the FARS-ADL are used to capture functional limitations from complementary perspectives and are applied in study participants aged 8 years and older. Although originally developed for Friedreich ataxia, the FARS-ADL is applicable across a range of ataxic and spastic movement disorders. Higher scores indicate greater functional impairment and reduced independence in daily activities.
Time frame: Through study completion, an average of 5 years, measured annually
Inventory of Non-Ataxia Signs - PLUS (INAS-PLUS)
INAS-PLUS is a clinician-reported inventory, derived from the original Inventory of Non-Ataxia Signs (INAS) and expanded by additional items, used to quantify the burden of neurological signs beyond core ataxia features in spastic and spastic-ataxic disorders.
Time frame: Through study completion, an average of 5 years, measured annually
MRC Sum Score for Muscle Strength
The Medical Research Council (MRC) Sum Score is a clinician-reported measure of global muscle strength based on standardized manual muscle testing across selected muscle groups. Individual muscle grades are summed to provide an overall estimate of muscle strength, with lower scores indicating greater weakness.
Time frame: Through study completion, an average of 5 years, measured annually
TreatHSP Quality of Life (TreatHSP-QoL)
The TreatHSP Quality of Life (TreatHSP-QoL) questionnaire is a disease-specific patient-reported outcome measure assessing health-related quality of life, including physical, functional, and psychosocial aspects, and is used in adults aged 18 years and older with hereditary spastic paraplegia and spastic ataxia.
Time frame: Through study completion, an average of 5 years, measured annually
Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Bochum, Germany
German Center for Neurodegenerative Diseases (DZNE) Bonn University Hospital Bonn Clinic for Parkinson's, sleep and movement disorders
Bonn, Germany
RECRUITINGGerman Center for Neurodegenerative Diseases (DZNE) Dresden; University Hospital Carl Gustav Carus Clinic and Polyclinic for Neurology
Dresden, Germany
RECRUITINGUniversity Hospital Erlangen, Department of Neurology
Erlangen, Germany
RECRUITINGUniversity Hospital Essen, Department of Pediatric Neurology / Institute of Human Genetics
Essen, Germany
RECRUITINGGerman Center for Neurodegenerative Diseases (DZNE) Göttingen
Göttingen, Germany
RECRUITINGUniversity Hospital Göttingen, Department of Neurology
Göttingen, Germany
RECRUITING...and 20 more locations
The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) is a caregiver-reported outcome measure developed for children and adolescents with motor disabilities. In this study, the CPCHILD is applied in all children aged 5 to 12 years, as well as in older individuals with cognitive impairment who are unable to reliably complete self-reported questionnaires.
Time frame: Through study completion, an average of 5 years, measured annually