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

NCT03206190 | Recruiting

• 1 other identifier: preSPG4
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Study goals

1. 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. 2.Biomarkers providing objective measures of disease activity

Conditions

Hereditary Spastic Paraplegia; Hereditary, Spastic Paraplegia, Autosomal Dominant

Keywords

SPG4; presymptomatic; at risk; mutation carriers; biomarkers; longitudinal progression

Outcome Measures

Primary Outcomes (1)

• 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)

  every two years, up to eight years

Secondary Outcomes (15)

• Subclinical progression (10m walking time)

  every two years, up to eight years

• Subclinical progression (5-stair climbing test time)

  every two years, up to eight years

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

  every two years, up to eight years

• MRI (not obligate) - DTI

  every two years, up to eight years

• MRI (not obligate) - volumetry

  every two years, up to eight years

Study Arms (3)

Mutation carrier

EXPERIMENTAL

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; 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

Non-mutation carrier

EXPERIMENTAL

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; 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

Known-mutation carriers but presymptomatic

EXPERIMENTAL

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; 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

Interventions

SPRS Score and clinical signs OTHER

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

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Cognition Testing using CANTAB BEHAVIORAL

Patients will be tested using the CANTAB

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Lumbar Puncture and blood draw DIAGNOSTIC_TEST

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

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

MRI DIAGNOSTIC_TEST

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

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Electrophysiology DIAGNOSTIC_TEST

Electrophysiological tests will be used to characterize patients better.

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Testing functional performance DIAGNOSTIC_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

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Non motor symptoms DIAGNOSTIC_TEST

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

Known-mutation carriers but presymptomatic; Mutation carrier; Non-mutation carrier

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen, Center for Neurology

Tübingen, 72076, Germany

RECRUITING

Related Publications (1)

• Rattay TW, Volker M, Rautenberg M, Kessler C, Wurster I, Winter N, Haack TB, Lindig T, Hengel H, Synofzik M, Schule R, Martus P, Schols L. The prodromal phase of hereditary spastic paraplegia type 4: the preSPG4 cohort study. Brain. 2023 Mar 1;146(3):1093-1102. doi: 10.1093/brain/awac155.

  PMID: 35472722 RESULT

MeSH Terms

Conditions

Spastic Paraplegia, Hereditary

Interventions

Spinal Puncture; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ludger Schöls, Prof.

  Head of Department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ludger Schöls, Prof.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Two Arms are blinded (mutation carriers vs. non mutation carriers) the third arm is an open-arm for presymptomatic tested mutation carriers
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: July 2, 2017
• Study Start: July 1, 2018
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: August 23, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)