Hereditary Spastic Paraplegia, Hereditary, Spastic Paraplegia, Autosomal Dominant
Conditions
Keywords
SPG4, presymptomatic, at risk, mutation carriers, biomarkers, longitudinal progression
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
Interventions
DIAGNOSTIC_TESTNon motor symptoms
By using a number of different tests we try to identify other non-motor symptoms which might manifest prior to disease onset.
OTHERSPRS Score and clinical signs
Patients will clinically characterized by using the SPRS Score and the inventory V3
BEHAVIORALCognition Testing using CANTAB
Patients will be tested using the CANTAB
DIAGNOSTIC_TESTLumbar Puncture and blood draw
Biomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF
DIAGNOSTIC_TESTMRI
MRI will be used to reveal presymptomatic brain morphology changes (not obligate)
DIAGNOSTIC_TESTElectrophysiology
Electrophysiological tests will be used to characterize patients better.
DIAGNOSTIC_TESTTesting 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
Sponsors
University Hospital Tuebingen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of a change of recognizable signs or symptoms | 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
| Measure | Time frame | Description |
|---|---|---|
| Subclinical progression (5-stair climbing test time) | 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)) | 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 | 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). |
| Cognition (MoCA) | every two years, up to eight years | To compare cognitive performance by using the Montreal Cognitive Assessment (MoCA) in mutation and non-mutation carriers |
| MRI (not obligate) - volumetry | 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 | 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) | 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. |
| Subclinical progression (10m walking time) | 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. |
| Non-motor symptoms (fatigue) | 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) | 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) | 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) | 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 | 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) | every two years, up to eight years | To compare cognitive performance by using the CANTAB battery in mutation and non-mutation carriers |
| Non-motor symptoms (quality of life) | 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. |
Countries
Germany
Contacts
Primary ContactLudger Schöls, Prof.
Outcome results
None listed