Network Properties as Biomarkers for Non-Invasive Brain Stimulation (NIBS) After Stroke

September 26, 2022 updated by: Robert Schulz, Universitätsklinikum Hamburg-Eppendorf

Evaluation of Cortico-Cerebellar Network Properties as Biomarkers for the Responsiveness to Cortico-Cerebellar Brain Stimulation in Stroke Patients

The present study will evaluate the potential of cortico-cerebellar network properties derived from neuroimaging in a group of chronic stroke patients to explain inter-subject variability in responsiveness to transcranial direct current stimulation (tDCS) targeting the cortico-spinal and cortico-cerebellar network.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Various studies have aimed to explore the potential of non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to promote motor recovery after stroke. After promising results from early proof-of-concept studies, particularly for the stimulation of the primary motor cortex (M1), it has become evident that the translation from scientific to clinical application is challenging. Aiming to uncover alternative stimulation targets, the cortico-cerebellar network and cerebellar brain stimulation have gained an increasing interest in the field of neurorehabilitation. However, large inter-study and inter-subject variability in behavioural responses to tDCS indicated that a one-size-fits-all approach might not lead to sufficient effect sizes in clinical populations. As structural and functional brain imaging has significantly evolved to powerful tools to assess distinct neuronal networks, such as the cortico-cerebellar network, in individual stroke patients and to infer structure-function-behaviour-relationships, the question arises whether such information might serve as imaging biomarkers to inform about the treatment responsiveness to non-invasive brain stimulation.

The present study will evaluate the potential of cortico-cerebellar network properties in a group of chronic stroke patients and healthy participants to explain inter-subject variability in responsiveness to two brain stimulation approaches targeting the cortico-spinal and cortico-cerebellar network: 1) cortical M1 tDCS, 2) combined M1 and cerebellar tDCS. Participants will be examined clinically and by structural and functional MRI. Structural MRI will be used to primarily reconstruct cortico-spinal and cortico-cerebellar motor tracts. Tract-related diffusion-based parameters will be used to infer microstructural network integrity. Resting-state MRI will be acquired to assess functional network connectivity. The behavioural impact of the tDCS will be evaluated during a multi-session structured motor training paradigm over seven days.

Recruitment:

Early- or late chronic stroke patients who have a persistent upper extremity deficit.

Treatment/Intervention:

Three tDCS montages combined with 7 days of physiotherapy (45min per session) will be applied to chronic stroke patients in a double-blinded, parallel group design. The following montages will be tested: anodal ipsilesional M1-stimulation with 2mA, anodal ipsilesion M1-stimulation combined with anodal contralesional cerebellar stimulation with 2mA per anode and a sham stimulation. The stimulation will be applied for the first 20min of physiotherapy.

Evaluation/Measurement:

Prior to the intervention, patients will receive functional testing and a MRI scan. 7 days after physiotherapy, functional testing will be performed again. Functional tests include: NIH Stroke Scale (NIHSS), Fugl Meyer Assessment of the upper limb (FMA), Wolf Motor Function Test (WMFT), Jebsen Taylor Hand Function Test (JTT), Nine-Hole-Peg-Test (NHP), Mini-Mental-State Examination.

Analyses:

Statistics will be conducted to relate neuroimaging-based network properties of the cortico-spinal and cortico-cerebellar network to the treatment gains under tDCS combined with motor training (primary outcome). Importantly, group differences regarding the behavioural effects of the verum and sham condition will serve as secondary outcomes.

Study Type

Interventional

Enrollment (Anticipated)

81

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Robert Schulz, PD Dr. med.
  • Phone Number: 0049-40-7410-0
  • Email: rschulz@uke.de

Study Locations

  • Germany
      • Hamburg, Germany, 20246
        • Recruiting
        • University Medical Center Hamburg-Eppendorf, Dept. of Neurology
        • Contact:
          • Robert Schulz, PD Dr. med.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients after first-ever clinical ischemic stroke in the early (>3 month) or later chronic (>6 months) stage of recovery
  • persistent motor deficit of the upper extremity
  • stroke location: supratentorial
  • age > 18 years
  • written informed consent obtained

Exclusion Criteria:

  • contraindication against MRI & tDCS
  • known epilepsy, previous epileptic seizure
  • electric implants such as brain stimulator
  • medical history suggesting more than one previous stroke
  • severe polyneuropathy and peripheral ischemic vascular diseases; only if they critically influence sensorimotor function of the upper limb
  • any active drug and alcohol abuse
  • any active and severe psychiatric disease (such as psychosis)
  • severe cognitive deficits (mini mental state examination, MMSE ≤ 23)
  • uncontrolled other medical problems (cardiovascular diseases, instable arrhythmia, arthritis)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Anodal M1 tDCS
20 minutes of anodal tDCS (C3 or C4 depending on side of lesion) to the ipsilesional M1: 2mA Combined with 45min of structured motor training.
Device: Transcranial direct current stimulation (tDCS)
Anodal stimulation or sham
ACTIVE_COMPARATOR: Combined M1 and cerebellar anodal tDCS
20 minutes of anodal tDCS (C3 or C4 depending on side of lesion) to the ipsilesional M1 combined with contralesional cerebellar montage (2cm lateral to Inion): 2mA per anode Combined with 45min of structured motor training.
Device: Transcranial direct current stimulation (tDCS)
Anodal stimulation or sham
SHAM_COMPARATOR: Sham tDCS
Sham stimulation. Combined with 45min of structured motor training.
Device: Transcranial direct current stimulation (tDCS)
Anodal stimulation or sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in FMA from baseline in the verum and sham conditions until last training day (Day 7)
Time Frame: Baseline - Day 7
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the FMA during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in FMA from baseline in the verum and sham conditions until 1 week after last training day (Day 14)
Time Frame: Baseline - Day 14
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the FMA during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in NIHSS from baseline in the verum and sham conditions until last training day (Day 7)
Time Frame: Baseline - Day 7
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the NIHSS during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in NIHSS from baseline in the verum and sham conditions until 1 week after last training day (Day 14)
Time Frame: Baseline - Day 14
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the NIHSS during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in WMFT from baseline in the verum and sham conditions until last training day (Day 7)
Time Frame: Baseline - Day 7
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in WMFT during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in WMFT from baseline in the verum and sham conditions until 1 week after last training day (Day 14)
Time Frame: Baseline - Day 14
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in WMFT during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in JTT from baseline in the verum and sham conditions until last training day (Day 7)
Time Frame: Baseline - Day 7
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in JTT during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in JTT from baseline in the verum and sham conditions until 1 week after last training day (Day 14)
Time Frame: Baseline - Day 14
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in JTT during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in NHP from baseline in the verum and sham conditions until last training day (Day 7)
Time Frame: Baseline - Day 7
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the NHP during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Relationship between properties of the cortico-spinal and cortico-cerebellar motor network and change in NHP from baseline in the verum and sham conditions until 1 week after last training day (Day 14)
Time Frame: Baseline - Day 14
Statistics will be conducted to relate single-patient data of structural and functional network properties to treatment gains in the NHP during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment effects for NIHSS on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and last training day (Day 7).
Time Frame: Baseline - Day 7
Statistics will be conducted to compare treament effects in NIHSS between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Treatment effects for FMA on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and last training day (Day 7).
Time Frame: Baseline - Day 7
Statistics will be conducted to compare treament effects in FMA between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Treatment effects for JTT on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and last training day (Day 7).
Time Frame: Baseline - Day 7
Statistics will be conducted to compare treament effects in JTT between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Treatment effects for WMFT on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and last training day (Day 7).
Time Frame: Baseline - Day 7
Statistics will be conducted to compare treament effects in WMFT between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Treatment effects for NHP on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and last training day (Day 7).
Time Frame: Baseline - Day 7
Statistics will be conducted to compare treament effects in NHP between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until last training day (Day 7). Statistics will be adjusted for baseline values.
Baseline - Day 7
Treatment effects for NIHSS on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and 1 week after last training day (Day 14).
Time Frame: Baseline - Day 14
Statistics will be conducted to compare treament effects in NIHSS between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Treatment effects for FMA on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and 1 week after last training day (Day 14).
Time Frame: Baseline - Day 14
Statistics will be conducted to compare treament effects in FMA between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Treatment effects for WMFT on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and 1 week after last training day (Day 14).
Time Frame: Baseline - Day 14
Statistics will be conducted to compare treament effects in WMFT between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Treatment effects for JTT on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and 1 week after last training day (Day 14).
Time Frame: Baseline - Day 14
Statistics will be conducted to compare treament effects in JTT between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14
Treatment effects for NHP on group level comparing M1 tDCS, M1-cerebellar tDCS and sham between baseline and 1 week after last training day (Day 14).
Time Frame: Baseline - Day 14
Statistics will be conducted to compare treament effects in NHP between groups during active and sham stimulations. Treatment gains will be defined as change from baseline until 1 week after last training day (Day 14). Statistics will be adjusted for baseline values.
Baseline - Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

German Research Foundation

Investigators

  • Principal Investigator: Robert Schulz, PD Dr. med., Universitätsklinikum Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2022

Primary Completion (ANTICIPATED)

July 1, 2024

Study Completion (ANTICIPATED)

July 1, 2024

Study Registration Dates

First Submitted

September 21, 2022

First Submitted That Met QC Criteria

September 26, 2022

First Posted (ACTUAL)

September 29, 2022

Study Record Updates

Last Update Posted (ACTUAL)

September 29, 2022

Last Update Submitted That Met QC Criteria

September 26, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MARK-NIBS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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