Stroke Therapy With Brain Oscillation Synchronized Stimulation (STROKEBOSS)

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Negative peak triggered 100 Hz triplet burst TMS; Device: 1 Hz rTMS

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • University Hospital Tübingen, Department for Neurology and Stroke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients are between 18 to 85 years old
2. Patient suffers from chronic stroke including hand/arm paresis and spasticity
3. Ipsilesional motor evoked potentials (MEPs) can be evoked (EMG > 50uV)
4. RMT of contralesional side < 70% maximum stimulator output (MSO)
5. Patient is willing to comply with the study restrictions.
6. Subject FMA-UE at the lesioned side is <= 60.

Exclusion Criteria

1. Patient is under the age of legal consent.
2. Patient has a history of seizure disorder.
3. 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).
4. Subject with intake of muscle-relaxing medication (e.g. baclofen, tizanidine, gabapentin,tolperisone, THC and derivates)
5. When spasticity is treated with botox there have to be at least tree months since the last injection
6. 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.
7. 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.
8. Patient has participated in another study within 2 weeks prior to the first study visit.
9. Patient is pregnant or trying to get pregnant.
10. Patient is unable to give informed consent.
11. Patient is unable to understand the instructions of the FMA-UE or not motivated to follow these instructions.
12. Patients who have contractions and therefore can't move.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts; 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.	Device: Negative peak triggered 100 Hz triplet burst TMS; MagVenture MagPro X100: Ipsilesional negative peak triggered 100 Hz triplet burst TMS.
Active Comparator: contralesional 1 Hz rTMS; 1200 stimuli to the contralesional primary motor cortex at 1 Hz. Stimulation intensity: 115% resting motor threshold.	Device: 1 Hz rTMS; MagVenture MagPro X100: Contralesional 1 Hz rTMS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)	Upper limb, affected side	Difference of score directly before intervention and score directly after intervention
Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)	Upper limb, affected side	Difference of score directly before intervention and score 3 months after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Wolf-Motor Function Test	Upper limb, affected side	Difference of score directly before intervention and score directly after intervention
Change in Modified Ashworth Scale	Upper limb, affected side	Difference of score directly before intervention and score directly after intervention
Change in PSAD spasticity assessment device score	Upper limb, affected side	Difference of score directly before intervention and score directly after intervention
Change in Resting-motor-threshold (RMT)	Hand knob, affected hemisphere	Difference of score directly before intervention and score directly after intervention

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Ulf Ziemann, Prof. Dr., University Hospital Tübingen, Department of Neurology and Stroke

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: August 10, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 2019-07, Version 4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No