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

Hereditary Spastic Paraplegia Clinical Trial

Official title:

Studying the Prodromal and Early Phase of Hereditary Spastic Paraplegia Type 4 (SPG4)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03206190
• Other study ID #: preSPG4
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2018
• Est. completion date: December 2031

Study information

• Verified date: August 2022
• Source: University Hospital Tuebingen
• Contact: Ludger Schöls, Prof.
• Phone: +49 7071 / 29
• Email: ludger.schoels[@]uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2031
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hereditary Spastic Paraplegia
• Hereditary, Spastic Paraplegia, Autosomal Dominant
• Muscle Spasticity
• Paraplegia
• Spastic Paraplegia, Hereditary

Intervention

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
• MRI
MRI will be used to reveal presymptomatic brain morphology changes (not obligate)
• Electrophysiology
Electrophysiological tests will be used to characterize patients better.
• 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
• 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.

Locations

Country	Name	City	State
Germany	University Hospital Tübingen, Center for Neurology	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Rattay TW, Völker M, Rautenberg M, Kessler C, Wurster I, Winter N, Haack TB, Lindig T, Hengel H, Synofzik M, Schüle R, Martus P, Schöls L. The prodromal phase of hereditary spastic paraplegia type 4: the preSPG4 cohort study. Brain. 2022 Apr 26. pii: awac — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: 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)	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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).	every two years, up to eight years
Secondary	MRI (not obligate) - volumetry	To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring brain volumetry.	every two years, up to eight years
Secondary	Nfl	To compare Nfl levels in serum (and cerebrospinal fluid (CSF) - not obligate) in mutation carriers and non-carriers.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	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).	every two years, up to eight years
Secondary	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.	every two years, up to eight years
Secondary	SPRS	To determine the sensitivity of the Spastic Paraplegia Rating Scale (SPRS) to detect the manifestation of disease onset as defined above.	every two years, up to eight years
Secondary	Cognition (CANTAB)	To compare cognitive performance by using the CANTAB battery in mutation and non-mutation carriers	every two years, up to eight years
Secondary	Cognition (MoCA)	To compare cognitive performance by using the Montreal Cognitive Assessment (MoCA) in mutation and non-mutation carriers	every two years, up to eight years