StrokeSTROKEBOSSNCT05005780
Stroke Therapy With Brain Oscillation Synchronized Stimulation
A study testing Negative peak triggered 100 Hz triplet burst TMS and 1 Hz rTMS in people with Stroke, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
This randomized, controlled, double-blind clinical pilot trial investigates the therapeutic potential of a novel personalized therapeutic brain-stimulation protocol in chronic stroke patients with spasticity. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke
- What is being tested?
- Negative peak triggered 100 Hz triplet burst TMS and 1 Hz rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 2 Oct 2019to 31 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are between 18 to 85 years old
- Patient suffers from chronic stroke including hand/arm paresis and spasticity
- Ipsilesional motor evoked potentials (MEPs) can be evoked (EMG > 50uV)
- RMT of contralesional side < 70% maximum stimulator output (MSO)
- Patient is willing to comply with the study restrictions.
- Subject FMA-UE at the lesioned side is <= 60.
Who cannot join
- Patient is under the age of legal consent.
- Patient has a history of seizure disorder.
- Patient with intake of pro-convulsive medication, e.g. , chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, MDMA (ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline, in accord with present consensus guidelines on safety, ethical considerations, and application of TMS in clinical practice and research (Rossi et al., 2009, 2021).
- Subject with intake of muscle-relaxing medication (e.g. baclofen, tizanidine, gabapentin,tolperisone, THC and derivates)
- When spasticity is treated with botox there have to be at least tree months since the last injection
- Patient has a cardiac pacemaker, implanted medication pump, intracardiac line, that is located close to (≤ 10 cm) to the location of activation of the TMS coil or acute, unstable cardiac disease.
Show all 12Show fewer
- Patient has an intracranial implant (e.g., aneurysm clips, shunts, stimula-tors, cochlear implants, or electrodes) or any other metal object that is located close to (≤ 10 cm) to the location of activation of the TMS coil (excluding the mouth) and that cannot be safely removed.
- Patient has participated in another study within 2 weeks prior to the first study visit.
- Patient is pregnant or trying to get pregnant.
- Patient is unable to give informed consent.
- Patient is unable to understand the instructions of the FMA-UE or not motivated to follow these instructions.
- Patients who have contractions and therefore can't move.
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Tübingen, Department for Neurology and Stroke
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: Stroke Therapy With Brain Oscillation Synchronized Stimulation: Randomized Controlled Pilot Study to Compare the Therapeutic Effectiveness of a Personalized EEG-triggered Repetitive High-frequency TMS Therapy Protocol With Standard Low-frequency TMS Therapy Protocol in Patients With Spastic Paresis
This randomized, controlled, double-blind clinical pilot trial investigates the therapeutic potential of a novel personalized therapeutic brain-stimulation protocol in chronic stroke patients with spasticity. Stroke patients will either receive ipsilesional 100 Hz transcranial magnetic stimulation (TMS) triplet burst protocol synchronized to the ongoing µ-alpha oscillation or contralesional 1 Hz repetitive TMS (rTMS) protocol. Motor recovery is assessed directly after as well as three months after completion of the therapy.
Read the detailed description
Stroke is one of the leading cause for long-term disability worldwide. The standard approach to treat deficits after stroke is a rehabilitation therapy, that follows the stroke event directly. This therapy mainly includes physiotherapy and occupational therapy. Yet, despite intensive rehabilitation efforts, more than half of all stroke patients remain greatly disabled.
Repetitive TMS is capable of inducing plasticity-like effects in the brain, that are expected to enhance adaptive plasticity processes leading to functional regain after stroke. In the motor cortex, brain oscillation-synchronized TMS, i.e. TMS triggered dependent on the phase of instantaneous µ-alpha oscillations as detected by real-time EEG (electroencephalography) analysis, has been shown to consistently increase motor cortical excitability and plasticity effects. We therefore hypothesis that a greater therapeutic potential of TMS to modulate dysfunctional brain networks can be exploited by personalizing TMS therapy to individual brain states (i.e. brain oscillations).
This study aims to investigate the effectiveness of an ipsilesional 100 Hz TMS triplet burst protocol synchronized to the ongoing µ-alpha oscillation compared to the current TMS standard therapy of contralesional 1 Hz rTMS in chronic stroke patients. Both groups will undergo stimulation therapy three times a week, with each session directly followed by physiotherapy. Motor recovery will be assessed directly after as well as three months after completion of the therapy.
- Conditions
- Stroke
- Being tested
- Negative peak triggered 100 Hz triplet burst TMS, 1 Hz rTMS
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Negative peak triggered 100 Hz triplet burst TMSDevice
MagVenture MagPro X100: Ipsilesional negative peak triggered 100 Hz triplet burst TMS.
1 Hz rTMSDevice
MagVenture MagPro X100: Contralesional 1 Hz rTMS.
| Study group | Role | What they receive |
|---|---|---|
| µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts | Experimental | µ-rhythm (The µ rhythm frequency band is defined by activity falling between 8 and 13 Hz and recorded by scalp electrodes over the sensorimotor cortex during waking neural activity) negative peak triggered TMS of ipsilesional primary motor cortex, consisting of 400 triple pulses at 100 Hz, delivered at a mean inter-triple pulse interval of 3.0 s. Stimulation intensity: 100% resting motor threshold. Receives: Device: Negative peak triggered 100 Hz triplet burst TMS |
| contralesional 1 Hz rTMS | Active comparator | 1200 stimuli to the contralesional primary motor cortex at 1 Hz. Stimulation intensity: 115% resting motor threshold. Receives: Device: 1 Hz rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)
Upper limb, affected side
Measured: Difference of score directly before intervention and score directly after intervention
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)
Upper limb, affected side
Measured: Difference of score directly before intervention and score 3 months after intervention
Secondary outcomes (4)
Change in Wolf-Motor Function Test
Upper limb, affected side
Measured: Difference of score directly before intervention and score directly after intervention
Change in Modified Ashworth Scale
Upper limb, affected side
Measured: Difference of score directly before intervention and score directly after intervention
Change in PSAD spasticity assessment device score
Upper limb, affected side
Measured: Difference of score directly before intervention and score directly after intervention
Change in Resting-motor-threshold (RMT)
Hand knob, affected hemisphere
Measured: Difference of score directly before intervention and score directly after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2021
- Study start2 Oct 2019
- Primary completion31 Aug 2022
- Study completion31 Aug 2022
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 StrokeStudies 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ulf Ziemann, Prof. Dr., Principal investigator, University Hospital Tübingen, Department of Neurology and Stroke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05005780
- Sponsor's protocol ID
- 2019-07, Version 4
- Acronym
- STROKEBOSS
- Status last verified
- Jul 2021
- First submitted
- 21 Jul 2021
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mahmoud W, Baur D, Zrenner B, Brancaccio A, Belardinelli P, Ramos-Murguialday A, Zrenner C, Ziemann U. Brain state-dependent repetitive transcranial magnetic stimulation for motor stroke rehabilitation: a proof of concept randomized controlled trial. Front Neurol. 2024 Aug 26;15:1427198. doi: 10.3389/fneur.2024.1427198. eCollection 2024.
PubMed 39253360
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stroke Therapy With Brain Oscillation Synchronized Stimulation: Randomized Controlled Pilot Study to Compare the Therapeutic Effectiveness of a Personalized EEG-triggered Repetitive High-frequency TMS Therapy Protocol With Standard Low-frequency TMS Therapy Protocol in Patients With Spastic Paresis
- ClinicalTrials.gov ID
- NCT05005780
- Acronym / sponsor ID
- STROKEBOSS / 2019-07, Version 4
- Conditions
- Stroke
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 16 Aug 2021 (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.
This randomized, controlled, double-blind clinical pilot trial investigates the therapeutic potential of a novel personalized therapeutic brain-stimulation protocol in chronic stroke patients with spasticity. Stroke patients will either receive ipsilesional 100 Hz transcranial magnetic stimulation (TMS) triplet burst protocol synchronized to the ongoing µ-alpha oscillation or contralesional 1 Hz repetitive TMS (rTMS) protocol. Motor recovery is assessed directly after as well as three months after completion of the therapy.
Detailed description
Stroke is one of the leading cause for long-term disability worldwide. The standard approach to treat deficits after stroke is a rehabilitation therapy, that follows the stroke event directly. This therapy mainly includes physiotherapy and occupational therapy. Yet, despite intensive rehabilitation efforts, more than half of all stroke patients remain greatly disabled.
Repetitive TMS is capable of inducing plasticity-like effects in the brain, that are expected to enhance adaptive plasticity processes leading to functional regain after stroke. In the motor cortex, brain oscillation-synchronized TMS, i.e. TMS triggered dependent on the phase of instantaneous µ-alpha oscillations as detected by real-time EEG (electroencephalography) analysis, has been shown to consistently increase motor cortical excitability and plasticity effects. We therefore hypothesis that a greater therapeutic potential of TMS to modulate dysfunctional brain networks can be exploited by personalizing TMS therapy to individual brain states (i.e. brain oscillations).
This study aims to investigate the effectiveness of an ipsilesional 100 Hz TMS triplet burst protocol synchronized to the ongoing µ-alpha oscillation compared to the current TMS standard therapy of contralesional 1 Hz rTMS in chronic stroke patients. Both groups will undergo stimulation therapy three times a week, with each session directly followed by physiotherapy. Motor recovery will be assessed directly after as well as three months after completion of the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts | Experimental | Device: Negative peak triggered 100 Hz triplet burst TMSµ-rhythm (The µ rhythm frequency band is defined by activity falling between 8 and 13 Hz and recorded by scalp electrodes over the sensorimotor cortex during waking neural activity) negative peak triggered TMS of ipsilesional primary motor cortex, consisting of 400 triple pulses at 100 Hz, delivered at a mean inter-triple pulse interval of 3.0 s. Stimulation intensity: 100% resting motor threshold. |
| contralesional 1 Hz rTMS | Active comparator | Device: 1 Hz rTMS1200 stimuli to the contralesional primary motor cortex at 1 Hz. Stimulation intensity: 115% resting motor threshold. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients are between 18 to 85 years old
- Patient suffers from chronic stroke including hand/arm paresis and spasticity
- Ipsilesional motor evoked potentials (MEPs) can be evoked (EMG > 50uV)
- RMT of contralesional side < 70% maximum stimulator output (MSO)
- Patient is willing to comply with the study restrictions.
Key exclusion criteria (12 listed)
- Patient is under the age of legal consent.
- Patient has a history of seizure disorder.
- Patient with intake of pro-convulsive medication, e.g. , chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, MDMA (ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline, in accord with present consensus guidelines on safety, ethical considerations, and application of TMS in clinical practice and research (Rossi et al., 2009, 2021).
- Subject with intake of muscle-relaxing medication (e.g. baclofen, tizanidine, gabapentin,tolperisone, THC and derivates)
- When spasticity is treated with botox there have to be at least tree months since the last injection
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 |
|---|---|---|
| Negative peak triggered 100 Hz triplet burst TMSMagVenture MagPro X100: Ipsilesional negative peak triggered 100 Hz triplet burst TMS. | Device | µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts |
| 1 Hz rTMSMagVenture MagPro X100: Contralesional 1 Hz rTMS. | Device | contralesional 1 Hz rTMS |
Primary outcome
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)
Time frame: Difference of score directly before intervention and score directly after intervention
Upper limb, affected side
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)
Time frame: Difference of score directly before intervention and score 3 months after intervention
Upper limb, affected side
4 secondary outcomes
Change in Wolf-Motor Function Test
Time frame: Difference of score directly before intervention and score directly after intervention
Change in Modified Ashworth Scale
Time frame: Difference of score directly before intervention and score directly after intervention
Change in PSAD spasticity assessment device score
Time frame: Difference of score directly before intervention and score directly after intervention
Change in Resting-motor-threshold (RMT)
Time frame: Difference of score directly before intervention and score directly after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
- Derived from this study: PubMed 39253360Mahmoud W, Baur D, Zrenner B, Brancaccio A, Belardinelli P, Ramos-Murguialday A, Zrenner C, Ziemann U. Brain state-dependent repetitive transcranial magnetic stimulation for motor stroke rehabilitation: a proof of concept randomized controlled trial. Front Neurol. 2024 Aug 26;15:1427198. doi: 10.3389/fneur.2024.1427198. eCollection 2024.
- Individual participant dataSharing planned: Undecided
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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.
Ulf Ziemann, Prof. Dr. principal investigator
University Hospital Tübingen, Department of Neurology and Stroke
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Negative peak triggered 100 Hz triplet burst TMS and 1 Hz rTMS in people with Stroke, 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 6 inclusion and 12 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 18 Aug 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 in Fugl-Meyer Assessment Upper Extremity (FMA-UE) (time frame: Difference of score directly before intervention and score directly after intervention). The study lists 2 primary outcomes in all. 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 NCT05005780, 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 18 Aug 2023.