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Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke (Boss-Stroke)

Primary Purpose

Ischemic Stroke, Acute

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Bossdevice
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke, Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: Subjects presenting with any of the following criteria will not be included in the trial: Hemorrhagic stroke (this refers to primary intracerebral hemorrhage only; hemorrhagic transformation of ischemic infarcts is not an exclusion criterion) 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 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 clinical trials or observation period of competing trials, if this participation affects the primary endpoint of the boss-stroke study. If the endpoint is not affected, participation is allowed. 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

Sites / Locations

  • Universitätsklinikum Frankfurt, Zentrum der Neurologie und Neurochirurgie
  • Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie
  • Uniklinik Köln, Klinik und Poliklinik für Neurologie
  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie
  • Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie
  • Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
  • Universitätsklinikum Tübingen, Klinik für NeurologieRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

No Intervention

Arm Label

Personalized stimulation

Non-personalized stimulation

Sham stimulation

Arm Description

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).

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Motor performance after 3 months
Motor performance 3 months after the intervention, as assessed by the FMA-UE
grip strength
Relative grip strength measured with a vigorimeter (measured in kg).
Assessment to measure quality of life
Stroke-Specific Quality-of-Life Scale (SS-QOL)
modified Rankin Scale Score
Rankin Scale Score (range 0-6, 0 = no disability, 6 =death)
Barthel Index
Barthel Index (ordinary scale ordinal scale 0-100, 0 = fully dependent, 100 =independent in feeding, walking and grooming)
inpatient/npatient rehabilitation
Number of days as an inpatient (in days) Number of days in inpatient rehabilitation (in days)

Full Information

First Posted
October 21, 2022
Last Updated
September 27, 2023
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT05600374
Brief Title
Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke
Acronym
Boss-Stroke
Official Title
Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
February 28, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
High-frequency rTMS will be applied to the ipsilesional motor cortex in 400 bursts of 100 Hz triplets with a mean inter-burst interval of 3 s (20 min treatment duration, 1,200 pulses per day) for 5 consecutive workdays (6,000 pulses total) at a stimulus intensity of 80% of resting motor threshold, in one of three conditions/arms, followed by 40 min task-specific hand/arm-physiotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Acute

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Multicenter randomized controlled double-blind three-arm parallel-group exploratory clinical trial Medical Device Regulation (MDR) clinical trail
Masking
ParticipantOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Personalized stimulation
Arm Type
Experimental
Arm Description
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).
Arm Title
Non-personalized stimulation
Arm Type
No Intervention
Arm Description
The identical rTMS protocol as in Arm 1, but 100 Hz triplets are not synchronized to the ongoing sensorimotor μ-oscillation.
Arm Title
Sham stimulation
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Bossdevice
Intervention Description
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.
Primary Outcome Measure Information:
Title
Motor performance after the intervention
Description
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.
Time Frame
After the last treatment session (5 days after first treatment)
Secondary Outcome Measure Information:
Title
Motor performance after 3 months
Description
Motor performance 3 months after the intervention, as assessed by the FMA-UE
Time Frame
3 months after the intervention
Title
grip strength
Description
Relative grip strength measured with a vigorimeter (measured in kg).
Time Frame
At screening and after 3 months after treatment
Title
Assessment to measure quality of life
Description
Stroke-Specific Quality-of-Life Scale (SS-QOL)
Time Frame
At screening and after 3 months after treatment
Title
modified Rankin Scale Score
Description
Rankin Scale Score (range 0-6, 0 = no disability, 6 =death)
Time Frame
At screening and after 3 months after treatment
Title
Barthel Index
Description
Barthel Index (ordinary scale ordinal scale 0-100, 0 = fully dependent, 100 =independent in feeding, walking and grooming)
Time Frame
At screening and after 3 months after treatment
Title
inpatient/npatient rehabilitation
Description
Number of days as an inpatient (in days) Number of days in inpatient rehabilitation (in days)
Time Frame
At screening and after 3 months after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Subjects presenting with any of the following criteria will not be included in the trial: Hemorrhagic stroke (this refers to primary intracerebral hemorrhage only; hemorrhagic transformation of ischemic infarcts is not an exclusion criterion) 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 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 clinical trials or observation period of competing trials, if this participation affects the primary endpoint of the boss-stroke study. If the endpoint is not affected, participation is allowed. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ulf Ziemann, Prof. Dr.
Phone
+49 7071 29
Ext
82049
Email
Ulf.Ziemann@med.uni-tuebingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Sven Poli, Dr.
Email
sven.poli@med.uni.tuebingen.de
Facility Information:
Facility Name
Universitätsklinikum Frankfurt, Zentrum der Neurologie und Neurochirurgie
City
Frankfurt a.M.
ZIP/Postal Code
60528
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Grefkes-Hermann, Prof. Dr.
Facility Name
Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Agnea Flöel, Prof. Dr.
Facility Name
Uniklinik Köln, Klinik und Poliklinik für Neurologie
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gereon R. Fink, Prof.Dr.
Facility Name
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Claßen, Prof. Dr.
Facility Name
Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sergiu Groppa, Prof. Dr.
Facility Name
Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonja Suntrup-Krueger, PD Dr.
Facility Name
Universitätsklinikum Tübingen, Klinik für Neurologie
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulf Ziemann, Prof. Dr

12. IPD Sharing Statement

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Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke

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