Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
- Conditions
- Hereditary Spastic Paraplegia
- Interventions
- Other: Clinical rating scale to measure disease severity and progressionDiagnostic Test: Next-Gen Sequencing (NGS)
- Registration Number
- NCT03981276
- Lead Sponsor
- Dr. Rebecca Schule
- Brief Summary
The aim of this study is to determine the clinical spectrum and natural progression of Hereditary Spastic Paraplegias (HSP) 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.
- Detailed Description
The investigators will perform a registry-based standardized prospective Natural History Study (NHS) in HSPs and related disorders. Participants will be seen annually. At study visits a standardized clinical examination will be performed including application of clinical rating scales (selection of rating scales may vary depending on the individual phenotype and specific genotype); data will be entered into a clinical database (HSP Registry; https://www.hsp-registry.net). At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy.
Optionally, additional examinations may be performed including imaging, quantitative movement analysis, neuropsychological examinations, analysis of patient or observer reported outcomes and OMICS analysis to characterize molecular biomarkers.
In participants without a genetic diagnosis, next generation sequencing may be performed.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Primary participant: Clinical rating scale to measure disease severity and progression Participants affected by hereditary spastic paraplegia (HSP) or a phenotypically related disorder Primary participants will be followed at annual intervals. The workup includes clinical, imaging, sensor-based, patient/observer reported and molecular outcome parameters and biosampling. Participants with unknown genetic diagnosis may receive genetic testing including whole exome or whole genome sequencing and other OMICS techniques. Primary participant: Next-Gen Sequencing (NGS) Participants affected by hereditary spastic paraplegia (HSP) or a phenotypically related disorder Primary participants will be followed at annual intervals. The workup includes clinical, imaging, sensor-based, patient/observer reported and molecular outcome parameters and biosampling. Participants with unknown genetic diagnosis may receive genetic testing including whole exome or whole genome sequencing and other OMICS techniques. Unrelated healthy control Next-Gen Sequencing (NGS) Unrelated healthy controls Healthy controls may undergo the same study procedures as primary participants. Secondary participant/ First or second-degree Next-Gen Sequencing (NGS) First or second degree unaffected family members of primary participants. Secondary participants may undergo the same study procedures as primary participants.
- Primary Outcome Measures
Name Time Method Change from baseline of Spastic Paraplegia Rating Scale (SPRS) total score at 2 years up to 2 years Disease severity will be assessed by application of the Spastic Paraplegia Rating Scale (SPRS), a clinical rating scale measuring disease severity in Hereditary Spastic Paraplegia (Schüle et al. Neurology 2006). The SPRS contains 13 items, each ranging from 0 to 4 points. The total score is calculated as the sum of all items, yielding a range for the total score between 0 and 52. Hereby, higher SPRS total scores indicate more severe disease.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (13)
University Medicine Essen
🇩🇪Essen, Germany
German Center for Neurodegenerative Diseases (DZNE) Rostock
🇩🇪Rostock, Germany
University Heidelberg
🇩🇪Heidelberg, Germany
University of Lübeck
🇩🇪Lübeck, Germany
German Center for Neurodegenerative Diseases (DZNE) München
🇩🇪München, Germany
University Innsbruck
🇦🇹Innsbruck, Austria
German Center for Neurodegenerative Diseases (DZNE) Bonn
🇩🇪Bonn, Germany
University of Erlangen
🇩🇪Erlangen, Germany
University Göttingen
🇩🇪Göttingen, Germany
German Center for Neurogedenerative Diseases (DZNE) Magdeburg
🇩🇪Magdeburg, Germany
University of Regensburg
🇩🇪Regensburg, Germany
University of Tübingen and German Center for Neurodegenerative Diseases (DZNE) Tübingen
🇩🇪Tübingen, Germany
IRCCS Medea Scientific Institute, Conegliano-PIeve di Soligo Research Centre
🇮🇹Pieve di Soligo, Italy