Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders

Dr. Rebecca Schule2,000 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

2,000

Conditions

Hereditary Spastic Paraplegia

Interventions

Clinical rating scale to measure disease severity and progressionOTHER

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.

Next-Gen Sequencing (NGS)DIAGNOSTIC_TEST

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

Eligibility

Sex: ALLHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria: * One of the following: 1. Primary participant: Clinical or genetic diagnosis of HSP or a related disorder 2. Secondary participant: Unaffected family member (1st or 2nd degree relative) of primary participant (with the above-mentioned restrictions for special populations) able to give informed consent 3. Unrelated healthy control able to give informed consent AND * Written informed consent AND \- Participants are willing and able to comply with study procedures Exclusion criteria: * Missing informed consent of primary or secondary participant/ healthy control/ legal representatives * For controls: evidence of a neurodegenerative disease or movement disorders; inability to give informed consent

Locations (13)

University Innsbruck

Innsbruck, Austria

RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Bonn

Bonn, Germany

Outcomes

Primary Outcomes

Change from baseline of Spastic Paraplegia Rating Scale (SPRS) total score at 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.

Time frame: up to 2 years

Central Contacts

Rebecca Schüle, PD Dr.

CONTACT

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

Ludger Schöls, Prof. Dr.

CONTACT

+49 7071 29 ludger.schoels@uni-tuebingen.de

Data from ClinicalTrials.gov

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