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

NCT ID: NCT03981276

Last Updated: 2021-05-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-10-14

Study Completion Date

2041-08-31

Brief Summary

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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

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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.

Conditions

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Hereditary Spastic Paraplegia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Clinical rating scale to measure disease severity and progression

Intervention Type 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.

Next-Gen Sequencing (NGS)

Intervention Type DIAGNOSTIC_TEST

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

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.

Next-Gen Sequencing (NGS)

Intervention Type DIAGNOSTIC_TEST

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

Unrelated healthy control

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

Next-Gen Sequencing (NGS)

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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Clinical rating scale to measure disease severity and progression

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.

Intervention Type OTHER

Next-Gen Sequencing (NGS)

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Spastic Paraplegia Rating Scale (SPRS)

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

German Center for Neurodegenerative Diseases (DZNE)

OTHER

Sponsor Role collaborator

Dr. Rebecca Schule

OTHER

Sponsor Role lead

Responsible Party

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Dr. Rebecca Schule

Principal Investigator, Leading Consultant

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rebecca Schüle, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Locations

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University Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Bonn

Bonn, , Germany

Site Status RECRUITING

University of Erlangen

Erlangen, , Germany

Site Status RECRUITING

University Medicine Essen

Essen, , Germany

Site Status RECRUITING

University Göttingen

Göttingen, , Germany

Site Status RECRUITING

University Heidelberg

Heidelberg, , Germany

Site Status NOT_YET_RECRUITING

University of Lübeck

Lübeck, , Germany

Site Status NOT_YET_RECRUITING

German Center for Neurogedenerative Diseases (DZNE) Magdeburg

Magdeburg, , Germany

Site Status RECRUITING

German Center for Neurodegenerative Diseases (DZNE) München

München, , Germany

Site Status RECRUITING

University of Regensburg

Regensburg, , Germany

Site Status NOT_YET_RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Rostock

Rostock, , Germany

Site Status NOT_YET_RECRUITING

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

Tübingen, , Germany

Site Status RECRUITING

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

Pieve di Soligo, , Italy

Site Status NOT_YET_RECRUITING

Countries

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Austria Germany Italy

Central Contacts

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Rebecca Schüle, PD Dr.

Role: CONTACT

+49 7071 29 ext. 85653

Ludger Schöls, Prof. Dr.

Role: CONTACT

+49 7071 29 ext. 85548

Facility Contacts

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Matthias Amprosi

Role: primary

+43 512 504 83686

Sylvia Bösch

Role: backup

+43 512 504 83686

Thomas Klockgether

Role: primary

+49 228 28715726

Susanne Seifert

Role: primary

+49 9131 85 44751

Pia-Marie Pryssok

Role: backup

+49 9131 85 44751

Sylwia Kante

Role: primary

+49 201 - 7236513

Anja Schadenberg

Role: primary

+49 551 39 10206

Heike Jacobi

Role: primary

+49 6221 - 56 - 7510

Maike Dümcke-Zilian

Role: primary

+49 451 3101 8215

Michaela Butryn

Role: primary

+49 391-67-13431

Jasmina Al-Tamami

Role: primary

+49 89 4400 57425

Zacharias Kohl

Role: primary

+49 941 941 3074

Christoph Kamm

Role: primary

+49 381 4944763

Katrin Dillmann

Role: primary

+49 7071 29 85653

Andrea Martinuzzi, MD

Role: primary

0438 414337

Related Links

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http://treathsp.net

Website of the TreatHSP consortium

http://hsp-registry.net

Website of the HSP Registry

Other Identifiers

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01GM1905

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HSP-PBP

Identifier Type: -

Identifier Source: org_study_id

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