The Pre-SPG4 Study

Sponsor:
University Hospital Tuebingen
Information provided by (Responsible Party):
Prof. Dr. Ludger Schöls, University Hospital Tuebingen

Purpose
Study goals

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
Biomarkers providing objective measures of disease activity

Condition: Hereditary Spastic Paraplegia

Intervention:
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: 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

Primary Outcome Measures:
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:

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

Secondary Outcome Measures:
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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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).

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.

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.

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

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

Estimated Enrollment: 200
Actual Study Start Date: June 12, 2017
Estimated Study Completion Date: May 2029
Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study: 18 Years to 70 Years (Adult, Senior)
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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03206190

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

Locations
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
Principal Investigator: Ludger Schöls, Prof. Head of Department
More Information

Responsible Party: Prof. Dr. Ludger Schöls, Prinicipal Investigator, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03206190 History of Changes
Other Study ID Numbers: pre-SPG4
Study First Received: June 21, 2017
Last Updated: July 2, 2017