Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders (HSP-PBP)

Dr. Rebecca Schule

Status: Enrolling

Conditions: Hereditary Spastic Paraplegia

Treatments: Diagnostic Test: Next-Gen Sequencing (NGS); Other: Clinical rating scale to measure disease severity and progression

Study type: Observational

Funder types: Other

Identifiers

NCT03981276

01GM1905 (Other Grant/Funding Number)

HSP-PBP

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,000 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

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

Trial design

2,000 participants in 3 patient groups

Primary participant:

Description:

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.

Treatment:

Other: Clinical rating scale to measure disease severity and progression

Diagnostic Test: Next-Gen Sequencing (NGS)

Secondary participant/ First or second-degree

Description:

First or second degree unaffected family members of primary participants. Secondary participants may undergo the same study procedures as primary participants.

Treatment:

Diagnostic Test: Next-Gen Sequencing (NGS)

Unrelated healthy control

Description:

Unrelated healthy controls Healthy controls may undergo the same study procedures as primary participants.

Treatment:

Diagnostic Test: Next-Gen Sequencing (NGS)