Hereditary Spastic ParaplegiaTreatHSPNCT07798674
TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias
An observational study of Hereditary Spastic Paraplegia and Spastic Ataxia, run by Heidelberg University at 30 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hereditary Spastic Paraplegia, Spastic Ataxia
- How many people
- 4,000 participants
- Where
- 30 sitesin 9 countries
- Study dates
- 16 Jul 2024to 31 Dec 2035
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study 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.
Who may be able to join
- General inclusion criteria:
- Age 5 or older
- Cohort 1: Affected
- Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype AND
- Alternative causes of phenotype excluded
- Cohort 2: Presymptomatic mutation carriers
Show all 10Show fewer
- Premanifest mutation carrier of (likely) pathogenic variant(s) in a disease gene associated with ataxia, spastic ataxia, HSP or related phenotype
- Cohort 3: Family controls - 1st or 2nd degree relative of a person with a clinical or genetic diagnosis of ataxia, spastic ataxia, HSP or related phenotype
- Cohort 4: Community controls
- Healthy individual unrelated to a person with neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype
Who cannot join
- 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.
- Current participation in an interventional clinical trial that may interfere with the objectives or outcome assessments of this observational study.
Trial locations and contacts
30 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 9 countries
Germany16 sites, 16 recruiting
- Recruiting
Ruhr University Bochum, Institute for Neuroinformatics (INI)
Bochum, 44801
Xenia Kobeleva, Prof. Dr., +49 (0) 234 32-28967, research@xenia-kobeleva.com
Xenia Kobeleva, Prof. Dr.
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Bonn University Hospital Bonn Clinic for Parkinson's, sleep and movement disorders
Bonn, 53127
Jennifer Faber, PD Dr., +49 (0)228 287-15736, Jennifer.Faber@dnze.de
Jennifer Faber, PD Dr.
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Dresden; University Hospital Carl Gustav Carus Clinic and Polyclinic for Neurology
Dresden, 01307
Falkenburger Björn, Prof. Dr., +49 351 458-2532, bjoern.falkenburger@dzne.de
Björn Falkenburger, Prof. Dr.
- Recruiting
University Hospital Erlangen, Department of Neurology
Erlangen, 91054
Regensburger Martin, Prof. Dr., +49 (0) 9131 85-39324, martin.regensburger@uk-erlangen.de
Martin Regensburger, Prof. Dr.
- Recruiting
University Hospital Essen, Department of Pediatric Neurology / Institute of Human Genetics
Essen, 45147
Bilge Albayrak, Dr., 49 (0) 201-723 2178, Bilge.Albayrak@uk-essen.de
Bilge Albayrak, Dr.
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Göttingen
Göttingen, 37075
Lisa Reinecke, Study Coordination, +49 (0) 551-39 61166, sz-umg.neurologie@med.uni-goettingen.de
Christoph van Riesen, Dr. med
- Recruiting
University Hospital Göttingen, Department of Neurology
Göttingen, 37075
Sandrin Plewe, Study Coordination, +49 (0) 551-39 64162, sandrin.plewe@med.uni-goettingen.de
Michael Sereda, Prof. Dr.
- Recruiting
University Medical Centre Göttingen, Clinic for Paediatric and Adolescent Medicine
Göttingen, 37075
Lara Marten, Dr., +49 (0) 551-39 67019, lara.marten@med.uni-goettingen.de
Lara Marten, Dr.
- Recruiting
University Hospital Heidelberg, Department of Neurology
Heidelberg, 69120
Perdita Beck, Study Coordinator, +4962215638121, Perdita.Beck@med.uni-heidelberg.de
Rebecca Schuele, Prof. Dr. med.
- Recruiting
Heidelberg University Hospital, Center for Child and Adolescent Medicine
Heidelberg, 69124
Stefan Kölker, Prof. Dr., +49 (0) 6221-56 4002, stefan.koelker@med.uni-heidelberg.de
Afshin Saffari, Dr.
- Recruiting
University Hospital Schleswig-Holstein , Department of Neurology
Kiel, 24105
Beate Lengl-Janssen, Dr. rer. nat., +49 (0) 431 500-24011, lotsinzsne.kiel@uksh.de
Tim W. Rattay, PD. Dr. med.
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Magdeburg, University Hospital Magdeburg, Department of Neurology
Magdeburg, 39120
Deike Hartmann, Study Coordination, +49 (0) 391/67-24535, deike.hartmann@dzne.de
Michaela Butryn, Dr.
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Munich, Munich University Hospital LMU, Department of Neurology
München, 80336
Büchner Boriana, Dr. (Study coordination), +49 (0)89 4400 57421, boriana.buechner@med.uni-muenchen.de
Thomas Klopstock, Prof. Dr.
- Recruiting
Klinikum Vest GmbH, Treatment Center Knappschafts Hospital Recklinghausen, NeuroCentrum - Department of Neurology, Stroke Unit and Early Rehabilitation
Recklinghausen, 45657
Nicole Jeschonneck, Study Coordination, +49 (0) 2361 56-83745, Nicole.Jeschonneck@Knappschaft-Kliniken.de
Stephan Klebe, Prof. Dr.
- Recruiting
University Hospital and Faculty of Medicine Tübingen, Clinic for Paediatrics and Adolescent Medicine
Tübingen, 72076
Hendrik Rosewich, +49 (0) 0201-723-2508, Hendrik.Rosewich@med.uni-tuebingen.de
Hendrik Rosenwich, Prof. Dr.
- Recruiting
University Hospital and Faculty of Medicine Tübingen, Neurology with a Focus on Neurodegenerative Diseases
Tübingen, 72076
Katrin Dillmann-Jehn, Study Coordination, +49 (0) 7071 29-85653, Katrin.Dillmann@med.uni-tuebingen.de
Ludger Schöls, Prof. Dr.
Italy5 sites, 5 recruiting
- Recruiting
IRCCS Fondazione Stella Maris, MEDMOL - Molecular Medicine, Neurogenetics and Neuromuscular Diseases
Calambrone, Pisa, 56018
Filippo Santorelli, Prof. Dr., +39 (0) 50 886238, filippo3364@gmail.com
Filippo Santorelli, Prof. Dr.
- Recruiting
Associazione La Nostra Famiglia - IRCCS Eugenio Medea
Conegliano, TV, 31015
Andrea Martinuzzi, Prof. Dr., +39 (0)438 - 414242, andrea.martinuzzi@lanostrafamiglia.it
Andrea Martinuzzi, Prof. Dr.
- Recruiting
University of Pisa, Azienda Ospedaliero Universitaria Pisana, Neurology
Pisa, 56126
Michelangelo Mancuso, Prof. Dr., +39 (0) 50 992443, michelangelo.mancuso@unipi.it
Michelangelo Mancuso, Prof. Dr.
- Recruiting
IRCCS Istituto Ospedale Pediatrico Bambino Gesù, Translational Pediatrics and Clinical Genetics
Roma, 00146
Enrico S Bertini, Prof. Dr., +39 (0) 668592104, enricosilvio.bertini@opbg.net
Enrico S Bertini, Prof. Dr.
- Recruiting
Università Cattolica del Sacro Cuore, Department of Neuroscience
Roma, 00168
Gabriella Silvestri, Prof. Dr., +39 (06) 30154338, Gabriella.Silvestri@unicatt.it
Gabriella Silvestri, Prof. Dr.
Spain3 sites, 3 recruiting
- Recruiting
Hospital Sant Joan de Déu Barcelona, Neuromuscular Diseases Unit
Barcelona, 08950
Laura Carrera Garcia, Dr., +34 (0) 93 253 21 00, laura.carrera@sjd.es
Laura Carrera Garcia, Dr.
- Recruiting
Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron University Hospital - Neurology Department
Barcelona
Alfons Macaya, Prof. Dr., +34 (0) 93 489 31 56, alfons.macaya@vallhebron.cat
Alfons Macaya, Prof. Dr.
- Recruiting
University Hospital Marqués de Valdecilla-IDIVAL, Department of Neurology
Santander, 39008
Jon Infante, MD, PhD, +34 (0) 616416622, jon.infante@scsalud.es
Jon Infante, MD, PhD
Austria1 site, 1 recruiting
- Recruiting
Medical University Innsbruck, Department of Neurology
Innsbruck, 6020
Sylivia Boesch, MSc, Priv. Doz. Dr., +43 512 504-83686, Sylvia.Boesch@i-med.ac.at
Sylivia Boesch, MSc, Priv. Doz. Dr.
Czechia1 site, 1 recruiting
- Recruiting
Centre of Hereditary Ataxias, Department of Neurology and Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol and Homolka University Hospital
Prague, 150 00
Jaroslava Paulasová Schwabova, M.D., Ph.D., +420 224 431 111, jaroslava.schwabova@fnmotol.cz
Jaroslava Paulasová Schwabova, M.D., Ph.D.
France1 site, 1 recruiting
- Recruiting
Paris 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, 75646
Hortense Hurmic, Clinical research assistant, +33 (0)157274606, hortense.hurmic@icm-institute.org
Alexandra Dürr, Prof. Dr.
Ireland1 site, 1 recruiting
- Recruiting
Tallaght University Hospital, Neurology
Dublin, Dublin 24
Sinead Murphy, MD, Prof., +353 1 414 4061, Sinead.Murphy@tuh.ie
Sinead Murphy, MD, Prof.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud university medical center - Radboundumc, University Medical Center
Nijmegen, 6525 GA
Bart van de Warrenburg, Prof. Dr., +31 (0) 24 361 11 11, Bart.vandeWarrenburg@radboudumc.nl
Bart van de Warrenburg, Prof. Dr.
Poland1 site, 1 recruiting
- Recruiting
University Hospital in Kraków, Neurology Clinical Department
Krakow, 30-688
Joanna Pera, Prof. Dr., +48 (0) 12 424 86 15, pera@su.krakow.pl
Joanna Pera, Prof. Dr.
About this study
Official title: TreatHSP/SPAX Master Protocol: Adaptive Platform for Longitudinal Progression, Biomarkers and Pathophysiology in Ataxias, Hereditary Spastic Paraplegias and Spastic Ataxias (TreatHSP/SPAX)
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Hereditary Spastic Paraplegia, Spastic Ataxia
- Keywords
- Hereditary Spastic Paraplegia, Ataxias, Hereditary, Spastic ataxia, Natural History Study, Patient Registry, Longitudinal Cohort Study, Platform Study, Adaptive Study Design, Disease Progression, Clinical Outcome Assessment, Biomarkers, Trial Readiness, Real-World Data
- Medical subject headings
- Spastic Paraplegia, Hereditary, Spastic Ataxia, Spinocerebellar Degenerations, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Affected | Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP and alternative cause of phenotype excluded | |
| Presymptomatic mutation carrier | Premanifest mutation carrier of (likely) pathogenic variant(s) in a disease gene associated with ataxia, spastic ataxia, HSP or related phenotype | |
| Family control | 1st or 2nd degree relative of a person with a clinical or genetic diagnosis of ataxia, spastic ataxia, HSP or related phenotype (group: Affected) | |
| Community control | Healthy individual unrelated to a person with neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Through study completion, an average of 5 years, measured annually
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, an average of 5 years, measured annually
Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
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.
Measured: Through study completion, an average of 5 years, measured annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2026
- Study start16 Jul 2024
- Primary completion31 Dec 2035 (estimated)
- Study completion31 Dec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Spastic ParaplegiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 4,000 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR), National Institute of Neurological Disorders and Stroke (NINDS), European Reference Network for Rare Neurological Diseases (ERN-RND), Horizon Europe, University Hospital Heidelberg
- Responsible party
- Principal investigator, Rebecca Schuele, University Hospital Heidelberg
- Investigators
- Rebecca Schuele, Prof. Dr. med., Principal investigator, Heidelberg University Hospital and Heidelberg Faculty of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07798674
- Sponsor's protocol ID
- S-317/2024 TreatHSP
- Other IDs
- 2R01NS072248, TreatHSP Registry
- Acronym
- TreatHSP
- Status last verified
- Aug 2026
- First submitted
- 30 Dec 2025
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data collected within the TreatHSP Master Protocol may be shared for secondary research purposes. Data eligible for sharing include selected clinical, functional, patient-reported, digital, imaging, and biomarker data generated within the TreatHSP/SPAX core study and approved adaptive substudies. Data sharing is subject to approval through the TreatHSP governance framework and requires submission of a scientific proposal, review by the Steering Committee, and execution of a data use agreement. Only pseudonymized data will be shared, and access will be limited to the minimum dataset necessary to address the approved research question. Data sharing will occur in compliance with applicable data protection regulations and participant consent.
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TreatHSP/SPAX Master Protocol: Adaptive Platform for Longitudinal Progression, Biomarkers and Pathophysiology in Ataxias, Hereditary Spastic Paraplegias and Spastic Ataxias (TreatHSP/SPAX)
- ClinicalTrials.gov ID
- NCT07798674
- Acronym / sponsor ID
- TreatHSP / S-317/2024 TreatHSP
- Conditions
- Hereditary Spastic Paraplegia, Spastic Ataxia
- Keywords
- Hereditary Spastic Paraplegia, Ataxias, Hereditary, Spastic ataxia, Natural History Study, Patient Registry, Longitudinal Cohort Study, Platform Study, Adaptive Study Design
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 4,000 participants (estimated)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR), National Institute of Neurological Disorders and Stroke (NINDS), European Reference Network for Rare Neurological Diseases (ERN-RND), Horizon Europe, University Hospital Heidelberg
- Study start
- 16 Jul 2024 (actual)
- Primary completion
- 31 Dec 2035 (estimated)
- Study completion
- 31 Dec 2035 (estimated)
- First posted
- 1 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Affected | – | –Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP and alternative cause of phenotype excluded |
| Presymptomatic mutation carrier | – | –Premanifest mutation carrier of (likely) pathogenic variant(s) in a disease gene associated with ataxia, spastic ataxia, HSP or related phenotype |
| Family control | – | –1st or 2nd degree relative of a person with a clinical or genetic diagnosis of ataxia, spastic ataxia, HSP or related phenotype (group: Affected) |
| Community control | – | –Healthy individual unrelated to a person with neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study 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.
Key inclusion criteria (10 listed)
- Age 5 or older
- Cohort 1: Affected
- Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype AND
- Alternative causes of phenotype excluded
- Cohort 2: Presymptomatic mutation carriers
Key exclusion criteria (5 listed)
- 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.
- Current participation in an interventional clinical trial that may interfere with the objectives or outcome assessments of this observational study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Modified Spastic Paraplegia Rating Scale
Time frame: Through study completion, an average of 5 years, measured annually
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.
Scale for the Assessment and Rating of Ataxia (SARA)
Time frame: Through study completion, an average of 5 years, measured annually
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.
SPAX Composite Scale (SPAXCOM)
Time frame: Through study completion, an average of 5 years, measured annually
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.
5 secondary outcomes
Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL)
Time frame: Through study completion, an average of 5 years, measured annually
Inventory of Non-Ataxia Signs - PLUS (INAS-PLUS)
Time frame: Through study completion, an average of 5 years, measured annually
MRC Sum Score for Muscle Strength
Time frame: Through study completion, an average of 5 years, measured annually
TreatHSP Quality of Life (TreatHSP-QoL)
Time frame: Through study completion, an average of 5 years, measured annually
Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
Time frame: Through study completion, an average of 5 years, measured annually
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- The TreatHSP website provides publicly accessible information on the TreatHSP Platform and the TreatHSP/SPAX study, including study objectives, participation information, and updates on ongoing research activities.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data collected within the TreatHSP Master Protocol may be shared for secondary research purposes. Data eligible for sharing include selected clinical, functional, patient-reported, digital, imaging, and biomarker data generated within the TreatHSP/SPAX core study and approved adaptive substudies. Data sharing is subject to approval through the TreatHSP governance framework and requires submission of a scientific proposal, review by the Steering Committee, and execution of a data use agreement. Only pseudonymized data will be shared, and access will be limited to the minimum dataset necessary to address the approved research question. Data sharing will occur in compliance with applicable data protection regulations and participant consent.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rebecca Schuele, Prof. Dr. med. principal investigator
Heidelberg University Hospital and Heidelberg Faculty of Medicine
30 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Spastic Paraplegia and Spastic Ataxia, run by Heidelberg University at 30 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Germany, Italy, Spain, Austria, Czechia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Perdita Beck, Study coordinator (+49 6221 56-38121, Perdita.Beck@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Spastic Paraplegia Rating Scale (time frame: Through study completion, an average of 5 years, measured annually). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.