The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4

N/ARecruitingNCT03206190

University Hospital Tuebingen200 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

TRIPLE

Enrollment

200

Conditions

Hereditary Spastic Paraplegia Hereditary, Spastic Paraplegia, Autosomal Dominant

Interventions

SPRS Score and clinical signsOTHER

Patients will clinically characterized by using the SPRS Score and the inventory V3

Cognition Testing using CANTABBEHAVIORAL

Patients will be tested using the CANTAB

Lumbar Puncture and blood drawDIAGNOSTIC_TEST

Biomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (1)

University Hospital Tübingen, Center for Neurology

Tübingen, Germany

RECRUITING

Outcomes

Primary Outcomes

Identification of a change of recognizable signs or symptoms

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)

Time frame: every two years, up to eight years

Secondary Outcomes

Subclinical progression (10m walking time)

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.

Time frame: every two years, up to eight years

Subclinical progression (5-stair climbing test time)

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.

Time frame: every two years, up to eight years

Subclinical progression (3 minute walking test (3MW))

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.

Time frame: every two years, up to eight years

MRI (not obligate) - DTI

To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring diffusion tensor imaging (DTI).

Time frame: every two years, up to eight years

MRI (not obligate) - volumetry

Central Contacts

Ludger Schöls, Prof.

CONTACT

+49 7071 / 29 ludger.schoels@uni-tuebingen.de

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

ElectrophysiologyDIAGNOSTIC_TEST

Electrophysiological tests will be used to characterize patients better.

Testing functional performanceDIAGNOSTIC_TEST

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

Non motor symptomsDIAGNOSTIC_TEST

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

To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring brain volumetry.

Time frame: every two years, up to eight years

Nfl

To compare Nfl levels in serum (and cerebrospinal fluid (CSF) - not obligate) in mutation carriers and non-carriers.

Time frame: every two years, up to eight years

Non-motor symptoms (SPRS inventory V3)

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.

Time frame: every two years, up to eight years

Non-motor symptoms (quality of life)

To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the EQ-5D.

Time frame: every two years, up to eight years

Non-motor symptoms (fatigue)

To identify clinical signs (other than spasticity) that are more frequent in mutation carriers than in non-carriers as recorded by the MFI.

Time frame: every two years, up to eight years

Non-motor symptoms (pain)

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.

Time frame: every two years, up to eight years

Non-motor symptoms (depression)

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).

Time frame: every two years, up to eight years

Non-motor symptoms (restless-legs)

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.

Time frame: every two years, up to eight years

SPRS

To determine the sensitivity of the Spastic Paraplegia Rating Scale (SPRS) to detect the manifestation of disease onset as defined above.

Time frame: every two years, up to eight years

Cognition (CANTAB)

To compare cognitive performance by using the CANTAB battery in mutation and non-mutation carriers

Time frame: every two years, up to eight years

Cognition (MoCA)

To compare cognitive performance by using the Montreal Cognitive Assessment (MoCA) in mutation and non-mutation carriers

Time frame: every two years, up to eight years