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The Pre-SPG4 Study

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ClinicalTrials.gov Identifier: NCT03206190
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : January 3, 2019
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Ludger Schöls, University Hospital Tuebingen

Tracking Information
First Submitted Date  ICMJE June 21, 2017
First Posted Date  ICMJE July 2, 2017
Last Update Posted Date January 3, 2019
Actual Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date May 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
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:
  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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03206190 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Pre-SPG4 Study
Official Title  ICMJE Studying the Presymptomatic and Early Phase of SPG4
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (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
Condition  ICMJE
  • Hereditary Spastic Paraplegia
  • Hereditary, Spastic Paraplegia, Autosomal Dominant
Intervention  ICMJE
  • 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
  • Diagnostic Test: MRI
    MRI will be used to reveal presymptomatic brain morphology changes (not obligate)
  • Diagnostic Test: Electrophysiology
    Electrophysiological tests will be used to characterize patients better.
  • Diagnostic Test: 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
  • Diagnostic Test: 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.
Study Arms  ICMJE
  • Experimental: Mutation carrier
    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.
    Interventions:
    • 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
  • Experimental: Non-mutation carrier
    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.
    Interventions:
    • 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
  • Experimental: Known-mutation carriers but presymptomatic
    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).
    Interventions:
    • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 29, 2017)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2029
Estimated Primary Completion Date May 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ludger Schöls, Prof. +49 7071 / 29 ext 82057 ludger.schoels@uni-tuebingen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03206190
Other Study ID Numbers  ICMJE pre-SPG4
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Prof. Dr. Ludger Schöls, University Hospital Tuebingen
Study Sponsor  ICMJE University Hospital Tuebingen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ludger Schöls, Prof. Head of Department
PRS Account University Hospital Tuebingen
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP