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

NCT03981276 | Recruiting

• 2 other identifiers: HSP-PBP01GM1905
• Study Type: observational
• Target: 2,000
• Locations: 3 countries
• Sites: 13

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.

Conditions

Hereditary Spastic Paraplegia

Keywords

Hereditary Spastic Paraplegia; Biomarker; Genetic etiology; Molecular mechanisms

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 2 years

Study Arms (3)

Primary participant:

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.

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

Secondary participant/ First or second-degree

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

Diagnostic Test: Next-Gen Sequencing (NGS)

Unrelated healthy control

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

Diagnostic Test: Next-Gen Sequencing (NGS)

Interventions

Clinical rating scale to measure disease severity and progression OTHER

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.

Also known as: Spastic Paraplegia Rating Scale (SPRS)

Primary participant:

Next-Gen Sequencing (NGS) DIAGNOSTIC_TEST

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

Primary participant:; Secondary participant/ First or second-degree; Unrelated healthy control

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Probands with a clinical or genetic diagnosis of an HSP and related disorders including pre-manifest individuals will be primarily enrolled in this study (primary participants). Additionally, unaffected family members of primary participants will be enrolled if they are of legal age (\>= 18 years) and able to give informed consent (secondary participants). Unaffected minors will only be enrolled under special circumstances as detailed in paragraph 5.1 (Special Populations - Unaffected minors). Lastly, healthy unrelated controls will be enrolled; these are necessary to contrast unspecific, gender- or age-related findings to disease specific findings.

You may qualify if:

• One of the following:
• Primary participant: Clinical or genetic diagnosis of HSP or a related disorder
• 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
• Unrelated healthy control able to give informed consent
• AND
• Written informed consent
• AND
• \- Participants are willing and able to comply with study procedures

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Rebecca Schule: lead
• German Federal Ministry of Education and Research: collaborator
• German Center for Neurodegenerative Diseases (DZNE): collaborator

Study Sites (13)

University Innsbruck

Innsbruck, 6020, Austria

RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Bonn

Bonn, 53127, Germany

RECRUITING

University of Erlangen

Erlangen, 91054, Germany

RECRUITING

University Medicine Essen

Essen, 45147, Germany

RECRUITING

University Göttingen

Göttingen, 37075, Germany

RECRUITING

University Heidelberg

Heidelberg, 69120, Germany

NOT YET RECRUITING

University of Lübeck

Lübeck, 23562, Germany

NOT YET RECRUITING

German Center for Neurogedenerative Diseases (DZNE) Magdeburg

Magdeburg, 39120, Germany

RECRUITING

German Center for Neurodegenerative Diseases (DZNE) München

München, 80336, Germany

RECRUITING

University of Regensburg

Regensburg, 93053, Germany

NOT YET RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Rostock

Rostock, 18147, Germany

NOT YET RECRUITING

University of Tübingen and German Center for Neurodegenerative Diseases (DZNE) Tübingen

Tübingen, 72076, Germany

RECRUITING

IRCCS Medea Scientific Institute, Conegliano-PIeve di Soligo Research Centre

Pieve di Soligo, 31053, Italy

NOT YET RECRUITING

Related Links

• Website of the TreatHSP consortium
• Website of the HSP Registry

Biospecimen

Retention: SAMPLES WITH DNA

optional biosample collection including blood (DNA, serum, plasma, RNA, PBMC), urine, CSF, skin biopsy

MeSH Terms

Conditions

Spastic Paraplegia, Hereditary

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Rebecca Schüle, PD Dr.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study 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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 20 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Leading Consultant

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 10, 2019
• Study Start: October 14, 2019
• Primary Completion (Estimated): August 1, 2039
• Study Completion (Estimated): August 1, 2041
• Last Updated: May 19, 2021

Record last verified: 2021-05

Locations

AU (1); IT (1); DE (11)