Hereditary Spastic ParaplegiaNCT03627416
Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
A study testing rTMS in people with Hereditary Spastic Paraplegia and Adrenomyeloneuropathy, run by Jakub Antczak at 1 site in Poland.
Trial summary
Hereditary spastic paraplegia (HSP) is the group of inherited disorders, characterized by progressive gait disturbance. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hereditary Spastic Paraplegia, Adrenomyeloneuropathy
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 sitePoland
- Study dates
- 9 Jan 2017to 1 Jan 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of hereditary spastic paraplegia - confirmed genetically, on the basis of family history or on exclusion or diagnosis of adrenomyeloneuropathy - confirmed genetically or by the elevated plasma very long chain fatty acid or on family history
- Gait disturbances affecting daily activities
- Ability to walk 10 meters without assistance or with crutches or with rollator walker
Who cannot join
- Presence of signs or symptoms indicating other than HSP or AMN ethiology of gait disturbances
- Contraindications for rTMS as listed by the Guidelines of the International Federation of Clinical Neurophysiology (IFCN 2009) i.e. seizure in the past, epilepsy, presence of magnetic material in the reach of magnetic field, pregnancy, likelihood to get pregnant, intracranial electrodes, cardiac pacemaker or intracardiac lines, frequent syncopes
Trial locations and contacts
1 site in 1 country.
Poland1 site
Jagiellonian University Medical College, Department of Neurology
Krakow, 31503
About this study
Official title: A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
Hereditary spastic paraplegia (HSP) is the group of inherited disorders, characterized by progressive gait disturbance. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity. The purpose of this study is to compare the effectiveness of rTMS in improving the HSP- and AMN-related gait disturbance and other symptoms with sham stimulation.
Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.
Read the detailed description
Hereditary spastic paraplegia (HSP) is a group of inherited disorders, characterized by progressive gait disturbance with weakness and spasticity, which predominate in lower extremities. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive method of modulation of brain plasticity proved to be effective in improving the gait performance in several conditions such as Parkinson Disease, vascular Parkinsonism, partial spinal cord injury and in post-stroke paresis. Previous studies documented also altered cortical excitability in HSP patients.
The purpose of this study is to compare the effectiveness of 10 hertz (Hz) rTMS over the primary motor cortices in improving the gait and strength and spasticity of lower extremities with sham stimulation in HSP and AMN patients.
Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.
- Being tested
- rTMS
- Keywords
- Hereditary spastic paraplegia, repetitive transcranial magnetic stimulation, disturbed gait, Adrenomyeloneuropthy
- Medical subject headings
- Spastic Paraplegia, Hereditary, Adrenoleukodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
high frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities
| Study group | Role | What they receive |
|---|---|---|
| active rTMS | Experimental | 10 hertz (Hz) rTMS will be administered over bilateral primary motor areas for the muscles of lower extremities. Therapy will include five daily sessions (on consecutive week days). In every sessions 3000 magnetic pulses of 90% of the resting motor threshold intensity will be elicited. Receives: Device: rTMS |
| Sham rTMS | Sham comparator | Sham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue. Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS
Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and directly after rTMS.
Measured: Before rTMS, directly (on the same day) after rTMS
Secondary outcomes (4)
Change in Timed up and go Test
Time of standing up from a chair, walking three metres to cross a line drawn 3 meters ahead and going back to sit down on the chair.
Measured: Baseline, directly (on the same day) after rTMS and 14 days later
Change in Medical Research Council Scale (MRC)
Change in bilateral assessment of the strength of following movements: hip flexion, knee flexion and extension, ankle flexion and extension. Assessment will be made according to six degrees (0 to 5) MRC scale, with higher values representing stronger movements, which is better outcome. Values are averaged from all movements tested.
Measured: Baseline, directly (on the same day) after rTMS and 14 days later
Modified Ashworth Scale
Bilateral assessment of spasticity in following movements: hip flexion, knee flexion and extension, ankle flexion and extension. Assessment will be made according to six degrees (0 to 5) Modified Ashworth Scale, with higher values representing more severe spasticity, which is worse outcome. Values are averaged from all movements tested.
Measured: Baseline, directly (on the same day) after rTMS and 14 days later
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS
Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and 14 days after finishing rTMS therapy.
Measured: Baseline, 14 days after rTMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2018
- Study start9 Jan 2017
- Primary completion1 Jan 2019
- Study completion1 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 16 patients with HSP or AMN will receive either active and sham stimulation in random order
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jakub Antczak
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jakub Antczak, Jagiellonian University
- Investigators
- Jakub M Antczak, MD, Principal investigator, Jagiellonian University Medical College, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03627416
- Sponsor's protocol ID
- JagiellonianU59
- Status last verified
- Aug 2021
- First submitted
- 23 Oct 2017
- Last updated
- 27 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
PubMed 19833552Antczak J, Pera J, Dabros M, Kozminski W, Czyzycki M, Wezyk K, Dwojak M, Banach M, Slowik A. The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia. Neural Plast. 2019 May 12;2019:7638675. doi: 10.1155/2019/7638675. eCollection 2019.
PubMed 31214256
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
- ClinicalTrials.gov ID
- NCT03627416
- Acronym / sponsor ID
- JagiellonianU59
- Keywords
- Hereditary spastic paraplegia, repetitive transcranial magnetic stimulation, disturbed gait, Adrenomyeloneuropthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Jakub AntczakUniversity, hospital or other
- Study start
- 9 Jan 2017 (actual)
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 1 Jan 2019 (actual)
- First posted
- 13 Aug 2018 (actual)
- Results
- Posted 27 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hereditary spastic paraplegia (HSP) is the group of inherited disorders, characterized by progressive gait disturbance. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity. The purpose of this study is to compare the effectiveness of rTMS in improving the HSP- and AMN-related gait disturbance and other symptoms with sham stimulation.
Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.
Detailed description
Hereditary spastic paraplegia (HSP) is a group of inherited disorders, characterized by progressive gait disturbance with weakness and spasticity, which predominate in lower extremities. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive method of modulation of brain plasticity proved to be effective in improving the gait performance in several conditions such as Parkinson Disease, vascular Parkinsonism, partial spinal cord injury and in post-stroke paresis. Previous studies documented also altered cortical excitability in HSP patients.
The purpose of this study is to compare the effectiveness of 10 hertz (Hz) rTMS over the primary motor cortices in improving the gait and strength and spasticity of lower extremities with sham stimulation in HSP and AMN patients.
Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- 16 patients with HSP or AMN will receive either active and sham stimulation in random order
| Arm | Type | Receives |
|---|---|---|
| active rTMS | Experimental | Device: rTMS10 hertz (Hz) rTMS will be administered over bilateral primary motor areas for the muscles of lower extremities. Therapy will include five daily sessions (on consecutive week days). In every sessions 3000 magnetic pulses of 90% of the resting motor threshold intensity will be elicited. |
| Sham rTMS | Sham comparator | Device: rTMSSham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- diagnosis of hereditary spastic paraplegia - confirmed genetically, on the basis of family history or on exclusion or diagnosis of adrenomyeloneuropathy - confirmed genetically or by the elevated plasma very long chain fatty acid or on family history
- Gait disturbances affecting daily activities
- Ability to walk 10 meters without assistance or with crutches or with rollator walker
Key exclusion criteria (2 listed)
- Presence of signs or symptoms indicating other than HSP or AMN ethiology of gait disturbances
- Contraindications for rTMS as listed by the Guidelines of the International Federation of Clinical Neurophysiology (IFCN 2009) i.e. seizure in the past, epilepsy, presence of magnetic material in the reach of magnetic field, pregnancy, likelihood to get pregnant, intracranial electrodes, cardiac pacemaker or intracardiac lines, frequent syncopes
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 |
|---|---|---|
| rTMShigh frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities | Device | Sham rTMS, active rTMS |
Primary outcome
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS
Time frame: Before rTMS, directly (on the same day) after rTMS
Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and directly after rTMS.
4 secondary outcomes
Change in Timed up and go Test
Time frame: Baseline, directly (on the same day) after rTMS and 14 days later
Change in Medical Research Council Scale (MRC)
Time frame: Baseline, directly (on the same day) after rTMS and 14 days later
Modified Ashworth Scale
Time frame: Baseline, directly (on the same day) after rTMS and 14 days later
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS
Time frame: Baseline, 14 days after rTMS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19833552Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
- Derived from this study: PubMed 31214256Antczak J, Pera J, Dabros M, Kozminski W, Czyzycki M, Wezyk K, Dwojak M, Banach M, Slowik A. The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia. Neural Plast. 2019 May 12;2019:7638675. doi: 10.1155/2019/7638675. eCollection 2019.
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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. This study is not recruiting at the moment.
Jakub M Antczak, MD principal investigator
Jagiellonian University Medical College, Department of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Hereditary Spastic Paraplegia and Adrenomyeloneuropathy, run by Jakub Antczak at 1 site in Poland.
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 2 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: finished, as of the sponsor's last update on 27 Sep 2021. 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 Poland. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 27 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS (time frame: Before rTMS, directly (on the same day) after rTMS). 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 NCT03627416, which also lists 2 linked publications.
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 27 Sep 2021.