NCT05600374

Brief Summary

We will investigate the therapeutic efficacy of EEG-synchronized noninvasive repetitive transcranial magnetic stimulation (rTMS) in the early subacute phase after ischemic stroke to improve upper limb motor rehabilitation. We hypothesize that synchronization of rTMS with the phase of the ongoing sensorimotor oscillation indicating high corticospinal excitability leads to significantly stronger improvement of paretic upper limb motor function than the same rTMS protocol non-synchronized to the ongoing sensorimotor oscillation or sham stimulation.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
144

participants targeted

Target at P75+ for not_applicable

Timeline
22mo left

Started Feb 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

4 active sites

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 Progress65%
Feb 2023Feb 2028

First Submitted

Initial submission to the registry

October 21, 2022

Completed
10 days until next milestone

First Posted

Study publicly available on registry

October 31, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

February 6, 2023

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2027

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2028

Last Updated

May 15, 2026

Status Verified

April 1, 2026

Enrollment Period

4.7 years

First QC Date

October 21, 2022

Last Update Submit

May 14, 2026

Conditions

Ischemic Stroke, Acute

Keywords

Oscillationmotor recoveryTranscranial magnetic stimulationEEG-synchronized

Outcome Measures

Primary Outcomes (1)

  • Motor performance after the intervention

    Primary efficacy endpoint is the motor performance after the intervention, as assessed by the Fugl-Meyer assessment (FMA-UE, range 0-66, 0 = no motor function, 66 = normal motor function) of the upper extremity (FMA-UE). The upper-extremity (UE) portion of the Fugl-Meyer assessment is the most frequently used scale to quantify post-stroke motor recovery of the upper extremity. The FMA-UE was used as an endpoint in most of the recent high-frequency rTMS trials in early subacute stroke patients.

    After the last treatment session (5 days after first treatment)

Secondary Outcomes (6)

  • Motor performance after 3 months

    3 months after the intervention

  • grip strength

    At screening and after 3 months after treatment

  • Assessment to measure quality of life

    At screening and after 3 months after treatment

  • modified Rankin Scale Score

    At screening and after 3 months after treatment

  • Barthel Index

    At screening and after 3 months after treatment

  • +1 more secondary outcomes

Study Arms (3)

Personalized stimulation

EXPERIMENTAL

Each 100 Hz triplet is triggered when a real-time analyzed EEG-defined state of high corticospinal excitability is detected (i.e., the negative peak of the ongoing sensorimotor \~10 Hz μ-oscillation).

Device: Bossdevice

Non-personalized stimulation

NO INTERVENTION

The identical rTMS protocol as in Arm 1, but 100 Hz triplets are not synchronized to the ongoing sensorimotor μ-oscillation.

Sham stimulation

NO INTERVENTION

The same protocol as in arm 1 synchronized to the EEG-defined high excitability state, but with ineffective rTMS, using the sham side of an active/placebo TMS coil designed for double-blind clinical trials. Conditions/arm 2 and 3 are control conditions. Arm 2 controls for the specific effect of Condition/arm 1 to synchronize stimulation to the ongoing μ-oscillation. Arm 3 tests if auditory or somatosensory inputs (which are identical in the real and sham stimulation conditions) synchronized with the ongoing μ-oscillation are relevant for the effects of Arm 1.

Interventions

BossdeviceDEVICE

The bossdevice is a real-time digital signal processor consisting of hardware and software algorithms. It is designed to read-in a real-time raw data stream from a bio-signal amplifier (electroencephalography, EEG), to continuously analyze this data and to detect patterns based on oscillations in different frequencies. When such a specific bio-signal pattern is detected, the device indicates this through a standard output port. This enables a connected device to know with millisecond accuracy when a specific biosignal pattern occurs.

Personalized stimulation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subjects meeting all of the following criteria will be considered for admission to the trial:
  • Age ≥ 18 years at the time of signing the informed consent.
  • Cerebral ischemia identified by brain imaging (cerebral MRI or CT) occurred 1-14 days ago.
  • Subject understands and voluntarily signs an informed consent document prior to any study related assessments/procedures.
  • Stroke has resulted in a new arm-/hand motor deficit with ≤ 50 points in the FMA-UE.
  • Presence of motor evoked potentials (MEPs) in the paretic hand. MEPs has to be obtained in the resting muscle
  • o If no MEPs can be obtained, MEP search procedure can be repeated later up to 14 days after stroke onset.
  • ● μ-oscillation (8-12 Hz) is recordable by EEG in the ipsilesional sensorimotor cortex with a sufficient signal-to-noise ratio of at least 3 dB
  • ● Subject is able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

  • Subjects presenting with any of the following criteria will not be included in the trial:
  • Estimated life expectancy \< 12 months
  • Presence of intracranial ferromagnetic metal (extracranial stents ≥10 cm away from the TMS coil are acceptable) in accordance with current safety guidelines \[18\]
  • Intraocular metal, cochlear implants
  • If TMS might interact with sensors of active implants (e.g., intra-cardiac defibrillators).
  • If a cranial bone gap affects currents induced by TMS (such as after craniotomy).
  • History of seizures or epilepsy.
  • Treatment intervention can't be started within 14 days after onset of stroke.
  • Women during pregnancy and lactation.
  • Participation in other studies if they are MDR or AMG studies or there is otherwise a high risk of insurance law issues intervening between two studies. In case of uncertainty, competing insurances must be contacted prior to participation
  • persistent addiction disorder (except for nicotine dependence)
  • CNS malignoma
  • If there is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason the investigator considers the subject inappropriate for participation in the study.
  • The ability to consent for patients who are unable to speak will be assessed on the basis of the NIHS-Score by an independent physician (details see chapter 21 and appendix).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Universitätsklinikum Frankfurt, Zentrum der Neurologie und Neurochirurgie

Frankfurt a.M., Frankfurt a.M., 60528, Germany

RECRUITING

Uniklinik Köln, Klinik und Poliklinik für Neurologie

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Münster, Klinik für Allgemeine Neurologie

Münster, 48149, Germany

RECRUITING

Universitätsklinikum Tübingen, Klinik für Neurologie

Tübingen, 72076, Germany

RECRUITING

Related Publications (1)

  • Lieb A, Zrenner B, Zrenner C, Kozak G, Martus P, Grefkes C, Ziemann U. Brain-oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double-blind three- arm parallel-group exploratory trial comparing personalized, non- personalized and sham repetitive transcranial magnetic stimulation (Acronym: BOSS-STROKE). BMC Neurol. 2023 May 25;23(1):204. doi: 10.1186/s12883-023-03235-1.

    PMID: 37231390DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Central Study Contacts

Ulf Ziemann, Prof. Dr.

CONTACT

+49 7071 29Ulf.Ziemann@med.uni-tuebingen.de

Sven Poli, Dr.

CONTACT

sven.poli@med.uni.tuebingen.de

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
The study is a multicenter randomized controlled double-blind three-arm parallel-group exploratory clinical trial. The subjects as well as the as the rater in the post- and the follow-up assessment will be blinded to the intervention condition the patient receives.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Multicenter randomized controlled double-blind three-arm parallel-group exploratory clinical trial Medical Device Regulation (MDR) clinical trail
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 21, 2022

First Posted

October 31, 2022

Study Start

February 6, 2023

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

February 28, 2028

Last Updated

May 15, 2026

Record last verified: 2026-04

Locations

DE(4)