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

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ClinicalTrials.gov Identifier: NCT03981276
Recruitment Status : Not yet recruiting
First Posted : June 10, 2019
Last Update Posted : June 13, 2019
Sponsor:
Collaborators:
German Federal Ministry of Education and Research
German Center for Neurodegenerative Diseases (DZNE)
Information provided by (Responsible Party):
Dr. Rebecca Schule, University Hospital Tuebingen

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.

Condition or disease Intervention/treatment
Hereditary Spastic Paraplegia Other: Clinical rating scale to measure disease severity and progression Diagnostic Test: Next-Gen Sequencing (NGS)

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.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 2000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 20 Years
Official Title: Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : August 2039
Estimated Study Completion Date : August 2041


Group/Cohort Intervention/treatment
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
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.
Other Name: Spastic Paraplegia Rating Scale (SPRS)

Diagnostic Test: Next-Gen Sequencing (NGS)
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.
Diagnostic Test: Next-Gen Sequencing (NGS)
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.
Diagnostic Test: Next-Gen Sequencing (NGS)
Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics




Primary Outcome Measures :
  1. Change from baseline of Spastic Paraplegia Rating Scale (SPRS) total score at 2 years [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
optional biosample collection including blood (DNA, serum, plasma, RNA, PBMC), urine, CSF, skin biopsy


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03981276


Contacts
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Contact: Rebecca Schüle, PD Dr. +49 7071 29 ext 85653 rebecca.schuele-freyer@uni-tuebingen.de
Contact: Ludger Schöls, Prof. Dr. +49 7071 29 ext 85548 ludger.schoels@uni-tuebingen.de

Locations
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Germany
University of Tübingen Not yet recruiting
Tübingen, Germany, 72076
Contact: Katrin Dillmann    +49 7071 29 85653    katrin.dillmann@med.uni-tuebingen.de   
Principal Investigator: Rebecca Schüle, MD         
Sub-Investigator: Ludger Schöls, MD         
Sponsors and Collaborators
Dr. Rebecca Schule
German Federal Ministry of Education and Research
German Center for Neurodegenerative Diseases (DZNE)
Investigators
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Principal Investigator: Rebecca Schüle, PD Dr. University Hospital Tübingen

Additional Information:
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Responsible Party: Dr. Rebecca Schule, Principal Investigator, Leading Consultant, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03981276     History of Changes
Other Study ID Numbers: HSP-PBP
01GM1905 ( Other Grant/Funding Number: Bundesministerium für Bildung und Forschung (BMBF) )
First Posted: June 10, 2019    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. Rebecca Schule, University Hospital Tuebingen:
Hereditary Spastic Paraplegia
Biomarker
Genetic etiology
Molecular mechanisms

Additional relevant MeSH terms:
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Muscle Spasticity
Paraplegia
Spastic Paraplegia, Hereditary
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Paralysis
Hereditary Sensory and Motor Neuropathy
Nervous System Malformations
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn