Hereditary Spastic ParaplegiaNCT03206190
The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
A study testing SPRS Score and clinical signs, Cognition Testing using CANTAB and Lumbar Puncture and blood draw in people with Hereditary Spastic Paraplegia and Hereditary, Spastic Paraplegia, Autosomal Dominant, run by University Hospital Tuebingen at 1 site in Germany.
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 Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hereditary Spastic Paraplegia, Hereditary, Spastic Paraplegia, Autosomal Dominant
- What is being tested?
- SPRS Score and clinical signs, Cognition Testing using CANTAB and Lumbar Puncture and blood draw
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jul 2018to Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Tübingen, Center for Neurology
Tübingen, 72076
Ludger Schöls, MD, +49 7071 29 82057, ludger.schoels@uni-tuebingen.de
Tim W. Rattay, MD
About this study
Official title: Studying the Prodromal and Early Phase of Hereditary Spastic Paraplegia Type 4 (SPG4)
Study goals
- 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
- Biomarkers providing objective measures of disease activity
- Being tested
- SPRS Score and clinical signs, Cognition Testing using CANTAB, Lumbar Puncture and blood draw, MRI, Electrophysiology
- Keywords
- SPG4, presymptomatic, at risk, mutation carriers, biomarkers, longitudinal progression
- Medical subject headings
- Spastic Paraplegia, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPRS Score and clinical signsOther
Patients will clinically characterized by using the SPRS Score and the inventory V3
Cognition Testing using CANTABBehavioural
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
MRIDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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). Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: every two years, up to eight years
Secondary outcomes (15)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: every two years, up to eight years
MRI (not obligate) - volumetry
To reveal alterations in brain morphology with magnetic resonance im-aging (MRI) in presymptomatic mutation carriers by measuring brain volumetry.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: every two years, up to eight years
Cognition (CANTAB)
To compare cognitive performance by using the CANTAB battery in mutation and non-mutation carriers
Measured: 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
Measured: every two years, up to eight years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start1 Jul 2018
- Primary completionDec 2029 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Spastic ParaplegiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Ludger Schöls, University Hospital Tuebingen
- Investigators
- Ludger Schöls, Prof., Principal investigator, Head of Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03206190
- Sponsor's protocol ID
- preSPG4
- Status last verified
- Aug 2022
- First submitted
- 21 Jun 2017
- Last updated
- 23 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35472722
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying the Prodromal and Early Phase of Hereditary Spastic Paraplegia Type 4 (SPG4)
- ClinicalTrials.gov ID
- NCT03206190
- Acronym / sponsor ID
- preSPG4
- Keywords
- SPG4, presymptomatic, at risk, mutation carriers, biomarkers, longitudinal progression
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study goals
- 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
- Biomarkers providing objective measures of disease activity
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mutation carrier | Experimental | 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 symptomsThe 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. |
| Non-mutation carrier | Experimental | 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 symptomsThe 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. |
| Known-mutation carriers but presymptomatic | Experimental | 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 symptomsIn 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). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPRS Score and clinical signsPatients will clinically characterized by using the SPRS Score and the inventory V3 | Other | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| Cognition Testing using CANTABPatients will be tested using the CANTAB | Behavioural | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| Lumbar Puncture and blood drawBiomaterial will be collected (not obligate) to compare e.g. Nfl levels in serum and CSF | Diagnostic test | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| MRIMRI will be used to reveal presymptomatic brain morphology changes (not obligate) | Diagnostic test | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| ElectrophysiologyElectrophysiological tests will be used to characterize patients better. | Diagnostic test | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| Testing functional performanceBy 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 | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
| Non motor symptomsBy using a number of different tests we try to identify other non-motor symptoms which might manifest prior to disease onset. | Diagnostic test | Known-mutation carriers but presymptomatic, Mutation carrier, Non-mutation carrier |
Primary outcome
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)
15 secondary outcomes
Subclinical progression (10m walking time)
Time frame: every two years, up to eight years
Subclinical progression (5-stair climbing test time)
Time frame: every two years, up to eight years
Subclinical progression (3 minute walking test (3MW))
Time frame: every two years, up to eight years
MRI (not obligate) - DTI
Time frame: every two years, up to eight years
MRI (not obligate) - volumetry
Time frame: every two years, up to eight years
Nfl
Time frame: every two years, up to eight years
Non-motor symptoms (SPRS inventory V3)
Time frame: every two years, up to eight years
Non-motor symptoms (quality of life)
Time frame: every two years, up to eight years
Non-motor symptoms (fatigue)
Time frame: every two years, up to eight years
Non-motor symptoms (pain)
Time frame: every two years, up to eight years
Non-motor symptoms (depression)
Time frame: every two years, up to eight years
Non-motor symptoms (restless-legs)
Time frame: every two years, up to eight years
SPRS
Time frame: every two years, up to eight years
Cognition (CANTAB)
Time frame: every two years, up to eight years
Cognition (MoCA)
Time frame: every two years, up to eight years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2022.
- Results publication: PubMed 35472722Rattay 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ludger Schöls, Prof. principal investigator
Head of Department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SPRS Score and clinical signs, Cognition Testing using CANTAB and Lumbar Puncture and blood draw in people with Hereditary Spastic Paraplegia and Hereditary, Spastic Paraplegia, Autosomal Dominant, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ludger Schöls, Prof. (+49 7071 / 29 ext. 82057, ludger.schoels@uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of a change of recognizable signs or symptoms (time frame: every two years, up to eight years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03206190, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2022.