TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age5+
SponsorHeidelberg University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype AND
Alternative causes of phenotype excluded
Disqualifiers
Presence of an alternative neurological or systemic condition that sufficiently explains the phenotype and is incompatible with ataxia, spastic ataxia, hereditary spastic paraplegia, or a related disorder.
Severe comorbidity or unstable medical condition that substantially interferes with study participation or interpretation of neurological and functional assessments.
Inability to comply with study procedures or follow-up requirements.
Lack of informed consent, including absence of consent by a legally authorized representative where required.
Trial population
Children, adolescents, and adults aged 5 years and older are recruited through multicenter, international participation from specialized neurology and genetics clinics, patient registries, affected families, and the general community. The study includes individuals with ataxia, spastic ataxia, hereditary spastic paraplegia, or related phenotypes; presymptomatic mutation carriers; first- or second-degree relatives of affected individuals; and neurologically healthy community controls.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
4,000 Participants
are grouped into 4 trial groupsGroup A: Affected
Group B: Presymptomatic mutation carrier
Group C: Family control
Group D: Community control
Trial outcomes
Primary outcomes
1
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 annually2
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 annually3
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 annuallySecondary outcomes
1
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 annually2
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 annually3
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 annually4
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 annuallyOther outcomes
1
FARS Functional Staging
The Friedreich Ataxia Rating Scale - Functional Staging (FARS-FS) is an ordinal measure of functional disease severity based on mobility and independence in activities of daily living. In this study, both a clinician-reported (ClinRO) version and a patient-reported (PROM) version of the FARS-FS are used to capture functional status from complementary perspectives. The FARS-FS serves as an anchor measure to support the determination and interpretation of clinically meaningful change in primary and secondary outcome measures over time.
Time frame
Through study completion, an average of 5 years, measured annually2
SPATAX Disability Stage
SPATAX Disability Stage is a clinician-reported ordinal staging system that categorizes overall disability based on mobility and functional dependence. It provides a global measure of disease severity and is used in this study as an anchor measure to support the interpretation of clinically meaningful change in primary and secondary outcomes.
Time frame
Through study completion, an average of 5 years, measured annually3
Clinical Global and Domain-Specific Impression of Severity and Change (CGI-S/CGI-C)
Clinical Global and Domain-Specific Impression of Severity and Change are clinician-reported assessments capturing overall disease severity and longitudinal change, as well as change within specific functional domains. The selected domains reflect disease impacts prioritized by individuals with SPAX diseases for their relevance to everyday life. These measures are used as anchor measures to contextualize and determine meaningful change in primary and secondary outcome measures.
Time frame
Through study completion, an average of 5 years, measured annually4
Patient-reported Global and Domain-Specific Impression of Severity and Change (PGI-S / PGI-C)
Patient-reported Global and Domain-Specific Impression of Severity and Change are self-reported assessments capturing overall disease severity and longitudinal change, as well as change within specific functional domains. The selected domains reflect disease impacts prioritized by individuals with SPAX diseases for their relevance to everyday life. These patient-reported measures are used as anchor measures to support the interpretation and determination of clinically meaningful change in primary and secondary outcome measures.
Time frame
Through study completion, an average of 5 years, measured annuallySponsors and contacts
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Heidelberg University
Lead sponsor
University Hospital Heidelberg
Sponsor institution
Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR)
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
European Reference Network for Rare Neurological Diseases (ERN-RND)
Collaborator
Horizon Europe
Collaborator
University Hospital Heidelberg
Collaborator
Source ClinicalTrials.gov