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Trial record 3 of 6 for:    SPG | "spastic paraplegia type 11" OR "Spastic Paraplegia, Hereditary" OR "Spastic Paraplegia"

The Pre-SPG4 Study

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ClinicalTrials.gov Identifier: NCT03206190
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : January 3, 2019
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Ludger Schöls, University Hospital Tuebingen

Brief Summary:

Study goals

  1. Prospective longitudinal data on progression in the natural course of SPG4 in presymptomatic mutation carriers prior to clinical disease onset and in early stages of disease
  2. Biomarkers providing objective measures of disease activity

Condition or disease Intervention/treatment Phase
Hereditary Spastic Paraplegia Hereditary, Spastic Paraplegia, Autosomal Dominant Other: SPRS Score and clinical signs Behavioral: Cognition Testing using CANTAB Diagnostic Test: Lumbar Puncture and blood draw Diagnostic Test: MRI Diagnostic Test: Electrophysiology Diagnostic Test: Testing functional performance Diagnostic Test: Non motor symptoms Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Two Arms are blinded (mutation carriers vs. non mutation carriers) the third arm is an open-arm for presymptomatic tested mutation carriers
Primary Purpose: Diagnostic
Official Title: Studying the Presymptomatic and Early Phase of SPG4
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : May 2027
Estimated Study Completion Date : May 2029


Arm Intervention/treatment
Experimental: Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
Other: SPRS Score and clinical signs
Patients will clinically characterized by using the SPRS Score and the inventory V3

Behavioral: Cognition Testing using CANTAB
Patients will be tested using the CANTAB

Diagnostic Test: Lumbar Puncture and blood draw
Biomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF

Diagnostic Test: MRI
MRI will be used to reveal presymptomatic brain morphology changes (not obligate)

Diagnostic Test: Electrophysiology
Electrophysiological tests will be used to characterize patients better.

Diagnostic Test: Testing functional performance
By using the 3 minute walk, 5 stair-climb test, and 10m walking test we will try to identify and measure subclinical progression prior to disease onset

Diagnostic Test: Non motor symptoms
By using a number of different tests we try to identify other non-motor symptoms which might manifest prior to disease onset.

Experimental: Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
Other: SPRS Score and clinical signs
Patients will clinically characterized by using the SPRS Score and the inventory V3

Behavioral: Cognition Testing using CANTAB
Patients will be tested using the CANTAB

Diagnostic Test: Lumbar Puncture and blood draw
Biomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF

Diagnostic Test: MRI
MRI will be used to reveal presymptomatic brain morphology changes (not obligate)

Diagnostic Test: Electrophysiology
Electrophysiological tests will be used to characterize patients better.

Diagnostic Test: Testing functional performance
By using the 3 minute walk, 5 stair-climb test, and 10m walking test we will try to identify and measure subclinical progression prior to disease onset

Diagnostic Test: Non motor symptoms
By using a number of different tests we try to identify other non-motor symptoms which might manifest prior to disease onset.

Experimental: Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
Other: SPRS Score and clinical signs
Patients will clinically characterized by using the SPRS Score and the inventory V3

Behavioral: Cognition Testing using CANTAB
Patients will be tested using the CANTAB

Diagnostic Test: Lumbar Puncture and blood draw
Biomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF

Diagnostic Test: MRI
MRI will be used to reveal presymptomatic brain morphology changes (not obligate)

Diagnostic Test: Electrophysiology
Electrophysiological tests will be used to characterize patients better.

Diagnostic Test: Testing functional performance
By using the 3 minute walk, 5 stair-climb test, and 10m walking test we will try to identify and measure subclinical progression prior to disease onset

Diagnostic Test: Non motor symptoms
By using a number of different tests we try to identify other non-motor symptoms which might manifest prior to disease onset.




Primary Outcome Measures :
  1. Identification of a change of recognizable signs or symptoms [ Time Frame: every two years, up to eight years ]

    Identification of recognizable signs or symptoms and their time course prior to disease-onset defined by the presence of a spastic gait and at least one of three additional features:

    1. manifest spasticity in the clinical examination (Ashworth Scale >0)
    2. positive Babinski sign
    3. pyramidal pattern of muscle weakness (e.g. hip abduction or foot elevation preferentially involved)


Secondary Outcome Measures :
  1. Subclinical progression (10m walking time) [ Time Frame: every two years, up to eight years ]
    To identify measures of subclinical progression of motor symptoms prior to disease onset by comparing functional performance in mutation carriers with that in individuals without mutation.

  2. Subclinical progression (5-stair climbing test time) [ Time Frame: every two years, up to eight years ]
    To identify measures of subclinical progression of motor symptoms prior to disease onset by comparing functional performance in mutation carriers with that in individuals without mutation.

  3. Subclinical progression (3 minute walking test (3MW)) [ Time Frame: every two years, up to eight years ]
    To identify measures of subclinical progression of motor symptoms prior to disease onset by comparing functional performance in mutation carriers with that in individuals without mutation.

  4. MRI (not obligate) - DTI [ Time Frame: every two years, up to eight years ]
    To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring diffusion tensor imaging (DTI).

  5. MRI (not obligate) - volumetry [ Time Frame: every two years, up to eight years ]
    To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring brain volumetry.

  6. Nfl [ Time Frame: every two years, up to eight years ]
    To compare Nfl levels in serum (and cerebrospinal fluid (CSF) - not obligate) in mutation carriers and non-carriers.

  7. Non-motor symptoms (SPRS inventory V3) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the SPRS inventory V3.

  8. Non-motor symptoms (quality of life) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the EQ-5D.

  9. Non-motor symptoms (fatigue) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the MFI.

  10. Non-motor symptoms (pain) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the Brief Pain Inventory.

  11. Non-motor symptoms (depression) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the Becks Depression Inventory (BDI).

  12. Non-motor symptoms (restless-legs) [ Time Frame: every two years, up to eight years ]
    To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the restless-legs diagnostic criteria questions.

  13. SPRS [ Time Frame: every two years, up to eight years ]
    To determine the sensitivity of the Spastic Paraplegia Rating Scale (SPRS) to detect the manifestation of disease onset as defined above.

  14. Cognition (CANTAB) [ Time Frame: every two years, up to eight years ]
    To compare cognitive performance by using the CANTAB battery in mutation and non-mutation carriers

  15. Cognition (MoCA) [ Time Frame: every two years, up to eight years ]
    To compare cognitive performance by using the Montreal Cognitive Assessment (MoCA) in mutation and non-mutation carriers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • First degree relatives (parents, offspring, and sibs) of SPG4 patients or symptomatic individuals with known SPAST mutation
  • Age 18 to 70 years
  • Written, informed consent (patient)

Exclusion Criteria:

  • No known SPAST-mutation within the family
  • Manifest spastic gait (subclinical signs like increased deep tendon reflexes, positive Babinski sign are allowed)
  • Participation in interventional trials

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): NCT03206190


Contacts
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Contact: Ludger Schöls, Prof. +49 7071 / 29 ext 82057 ludger.schoels@uni-tuebingen.de

Locations
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Germany
University Hospital Tübingen, Center for Neurology Recruiting
Tübingen, Germany, 72076
Contact: Ludger Schöls, MD    +49 7071 29 82057    ludger.schoels@uni-tuebingen.de   
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
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Principal Investigator: Ludger Schöls, Prof. Head of Department

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Responsible Party: Prof. Dr. Ludger Schöls, Prinicipal Investigator, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03206190     History of Changes
Other Study ID Numbers: pre-SPG4
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: January 3, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Prof. Dr. Ludger Schöls, University Hospital Tuebingen:
SPG4
presymptomatic
at risk
mutation carriers
biomarkers
longitudinal progression

Additional relevant MeSH terms:
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Spastic Paraplegia, Hereditary
Muscle Spasticity
Paraplegia
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