Clinical trial NCT03981276: Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
Official title: Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Spastic Paraplegia
Keywords: Hereditary Spastic Paraplegia
Biomarker
Genetic etiology
Molecular mechanisms
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
name: German Center for Neurodegenerative Diseases (DZNE)
First posted: 2019-06-10
Enrollment: 2000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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

Primary outcomes:
measure: Change from baseline of Spastic Paraplegia Rating Scale (SPRS) total score at 2 years
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: University Innsbruck
city: Bonn
country: Germany
facility: German Center for Neurodegenerative Diseases (DZNE) Bonn
city: Erlangen
country: Germany
facility: University of Erlangen
city: Essen
country: Germany
facility: University Medicine Essen
city: Göttingen
country: Germany
facility: University Göttingen
city: Heidelberg
country: Germany
facility: University Heidelberg
city: Lübeck
country: Germany
facility: University of Lübeck
city: Magdeburg
country: Germany
facility: German Center for Neurogedenerative Diseases (DZNE) Magdeburg
city: München
country: Germany
facility: German Center for Neurodegenerative Diseases (DZNE) München
city: Regensburg
country: Germany
facility: University of Regensburg
city: Rostock
country: Germany
facility: German Center for Neurodegenerative Diseases (DZNE) Rostock
city: Tübingen
country: Germany
facility: University of Tübingen and German Center for Neurodegenerative Diseases (DZNE) Tübingen
city: Pieve di Soligo
country: Italy
facility: IRCCS Medea Scientific Institute, Conegliano-PIeve di Soligo Research Centre
Study officials:
affiliation: University Hospital Tübingen
name: Rebecca Schüle, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References: