NCT06116942

Brief Summary

The goal of the present clinical trial is to explore whether an innovative technology-based approach can help individuals who have had a stroke and can no longer move their hands with ease. Our approach consists of a combination of two technologies: Transcranial Magnetic Stimulation (TMS) and a Brain-Computer Interface (BCI). The former entails the application of magnetic fields over the head to stimulate the brain preparing it for a better ability to produce movement. The latter consists of measuring brain activity to personalize a type of computer-based training that is designed to increase communication between the brain and the muscles.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for not_applicable

Timeline
16mo left

Started Nov 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress66%
Nov 2023Sep 2027

First Submitted

Initial submission to the registry

September 27, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

November 3, 2023

Completed
5 days until next milestone

Study Start

First participant enrolled

November 8, 2023

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 19, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 19, 2027

Last Updated

November 9, 2023

Status Verified

October 1, 2023

Enrollment Period

2.9 years

First QC Date

September 27, 2023

Last Update Submit

November 8, 2023

Conditions

Keywords

Transcranial Magnetic StimulationIntermittent Theta Burst StimulationBrain-Computer InterfaceRehabilitationEEGMRIMolecular changesBrain plasticityStrokeHemiparesis

Outcome Measures

Primary Outcomes (3)

  • Motor-evoked potential (MEP) parameters

    An MEP is the electromyography response to a single TMS pulse delivered over the motor cortex, over the representation of multiple muscles. MEP changes will be evaluated with a mixed effects model. mixed-effects model. The model will consider the Patient, Period, Treatment (stimulation type) and Session number. The Period\*Treatment interaction will be verified to detect carry-over effects. The investigators expect to observe a main effect of Treatment and Session number.

    Measured two times per day, at the days: 3-12 and 15-24. The first measurement is performed immediately before the rTMS-BCI intervention and the second immediately after the rTMS-BCI intervention.

  • Fugl-Meyer upper extremity assessment of sensorimotor function

    Quantitative evaluation of motor, balance, sensation and joint functions. The sums of values recorded before and after the stimulation periods will be fed into an unpaired sample t-test to evaluate carryover effects whereas the differences observed between recordings before and after the stimulation will be fed into an unpaired sample t-test for the evaluation of initial evidence of the effect of rTMS.

    Measured one time at day, at the days: 2, 13, 14, and 25.

  • Event-related desynchronization (ERD)

    Electroencephalography (EEG) will be recorded during a cued motor task. This data will be used to calculate event-related de-synchronization, defined as the difference in signal power in the miu (8-12 Hz) and beta bands (13-30 Hz) between a baseline period prior to the cue and a post-cue period. Changes in ERD will be evaluated with permutation-based statistics.

    Measured one time per day, at the days: 2, 13, 14, and 25.

Secondary Outcomes (8)

  • Brain-Computer Interface accuracy

    Measured one time per day, at days 3-12 and days 15-24.

  • Task-related functional Magnetic Resonance Imaging (t-fMRI)

    Measured one time per day, at the days 2, 13, 14, and 25.

  • Jebsen-Taylor Hand Function Test

    Measured one time per day, at the days 2, 13, 14, and 25.

  • Diffusion-based tractography

    Measured one time per day, at the days 2, 13, 14, and 25.

  • Movement-related cortical potential amplitude

    Measured one time per day, at the days 2, 13, 14, and 25.

  • +3 more secondary outcomes

Other Outcomes (8)

  • Adherence

    Through study completion, for 25 days.

  • Upper extremity motor activity log (UE-MAL)

    Measured one time per day, at days 2, 13, 14, and 25.

  • Withdrawal rate

    Through study completion, for 25 days.

  • +5 more other outcomes

Study Arms (2)

Active stimulation - Placebo stimulation

EXPERIMENTAL

Participants will undergo a 2 intervention periods. The first intervention period will consist of a 2-week course of rTMS followed by BCI-mediated training. This intervention will be succeeded by a 4-week washout period to mitigate any carry-over effects. The second intervention period will entail 2 weeks of sham rTMS followed by BCI-mediated training.

Device: Active rTMSDevice: Sham rTMS

Placebo stimulation - Active stimulation

EXPERIMENTAL

Participants will undergo the same interventions as the first arm but delivered in inverse order. The first intervention period will consist of 2 weeks of sham rTMS followed by BCI-mediated training. The second intervention period will entail 2 weeks of rTMS prior to BCI-mediated training and will start after a 4-weeks washout period.

Device: Active rTMSDevice: Sham rTMS

Interventions

The Transcranial Magnetic Stimulation will consist of placing a figure-of-eight shape coil of wire over the head of the participants. Then, a brief electric current will pass through the coil, inducing a magnetic field capable of stimulating neurons located beneath the coil. For the active coil, the maximal stimulation intensity is reached beneath the center of the coil. In the present study, the intermittent theta-burst protocol will be implemented. This protocol is expected to modulate the excitability of the brain, priming it for a stronger activation of the motor-related brain areas engaged during brain-computer interface-based training. The structural MRI of each participant will be used to guide neuronavigation towards ipsilesional motor areas.

Also known as: Intermittent Theta Burst Stimulation, Repetitive Transcranial Magnetic Stimulation, iTBS
Active stimulation - Placebo stimulationPlacebo stimulation - Active stimulation
Sham rTMSDEVICE

To implement a placebo stimulation, a sham coil will be used to deliver the same stimulation protocol. The sham coil is identical in dimensions and weight to the active coil but produces a diminished magnetic field. For the sham coil, the stimulation intensity is minimal beneath the center of the coil, the same area with the highest intensity during stimulation with an active coil. The structural MRI scan of each participant will be used to guide neuronavigation towards the same area where the active stimulation was applied.

Also known as: Placebo Intermittent Theta Burst Stimulation, Placebo Repetitive Transcranial Magnetic Stimulation, Sham iTBS
Active stimulation - Placebo stimulationPlacebo stimulation - Active stimulation

Eligibility Criteria

Age20 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of a subcortical stroke at least 6 months before the initiation of the trial and confirmed with magnetic resonance imaging (MRI) or computed tomography
  • Present moderate to severe hemiparesis in an upper limb
  • Language comprehension as well as visual and auditory perception sufficient to engage in Brain Computer Interface training
  • Age from 20 to 80 years old
  • Clear consciousness and stable vital signs
  • Eligible for MRI, EEG, BCI and TMS methods

You may not qualify if:

  • Drug abuse or recent changes in medications that may alter the central nervous system when the measurements begin or during the measurements (e.g., benzodiazepines, serotoninergic and dopaminergic agents)
  • History of seizure
  • Bone, joint and muscle diseases
  • Peripheral neuropathy or other neurological or psychiatric diseases (including, tinnitus, migraine, or mood disorders with the exception of minimal, mild, and moderate depression, reflected as a Beck depression scale score lower than 29).
  • Strong cognitive deficits (including speech, attention, hearing, vision, sensation or intelligence deficits) reflected as a Montreal Cognitive Assessment (MoCA) score lower or equal to 24
  • Lesions in the upper extremities
  • Bone, joint and muscle diseases
  • Severe spasticity (higher than 3) or pain in the upper limb and affecting wrist extension
  • Contraindications of undergoing TMS examinations: history of seizures, history of epilepsy, unclear unconsciousness, migraines or metals on the head
  • Contraindications for MRI: metals in the body, metallic prosthetics or claustrophobia
  • Participation in other interventional trials using BCI or rTMS within less than 6 months ago
  • Participation in another interventional clinical trial
  • Suspected lack of compliance
  • Pregnant or nursing women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Max Planck Institute for Human Cognitive and Brain Sciences

Leipzig, Saxony, 04103, Germany

RECRUITING

Related Publications (2)

  • Tang Z, Han K, Wang R, Zhang Y, Zhang H. Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis. Front Neurol. 2022 Jun 20;13:918597. doi: 10.3389/fneur.2022.918597. eCollection 2022.

    PMID: 35795793BACKGROUND
  • Peng Y, Wang J, Liu Z, Zhong L, Wen X, Wang P, Gong X, Liu H. The Application of Brain-Computer Interface in Upper Limb Dysfunction After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Hum Neurosci. 2022 Mar 29;16:798883. doi: 10.3389/fnhum.2022.798883. eCollection 2022.

    PMID: 35422693BACKGROUND

Related Links

MeSH Terms

Conditions

StrokeParesis

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Aimee Flores-Sandoval, MsC

    Charité Universitätmedizin Berlin and Max Planck Institute for Human Cognitive and Brain Sciences

    STUDY CHAIR
  • Arno Villringer, MD PhD

    Max Planck Institute for Human Cognitive and Brain Sciences

    STUDY DIRECTOR
  • Bernhard Sehm, PD. med.

    Max Planck Institute for Human Cognitive and Brain Sciences and Halle University

    PRINCIPAL INVESTIGATOR
  • Vadim Nikulin, PhD.

    Max Planck Institute for Human Cognitive and Brain Sciences

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Aimee Arely Flores Sandoval, MsC

CONTACT

Arno Villringer, MD PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: Randomized placebo-controlled cross-over factorial single-blind mono-center trial with 2 arms (active stimulation-placebo stimulation \| placebo stimulation-active stimulation).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 27, 2023

First Posted

November 3, 2023

Study Start

November 8, 2023

Primary Completion (Estimated)

September 19, 2026

Study Completion (Estimated)

September 19, 2027

Last Updated

November 9, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will share

Data sharing will require approval by the local ethics committee (EC) of the researcher requesting the data along with public registration of the study. Data sharing will also be subject to compliance with the European Union General Data Protection Regulation.

Shared Documents
STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
Time Frame
After the end of the study and for 10 years
Access Criteria
The purpose for requesting the data and planned analysis must comply with the General Data Protection Regulation as well as Medical device regulation of the European Union.

Locations