Patient-tailored Transcranial Direct Current Stimulation to Improve Stroke Rehabilitation (PRACTISE)
Primary Purpose
Ischemic Stroke, Upper Extremity Hemiparesis
Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Active Transcranial Direct Current Stimulation
Sham stimulation
Sponsored by
About this trial
This is an interventional supportive care trial for Ischemic Stroke focused on measuring non-invasive brain stimulation, transcranial direct current stimulation, effective connectivity, functional connectivity, Fugl-Meyer Assessment, Functional Magnetic Resonance Imaging
Eligibility Criteria
Patients - Inclusion Criteria:
- Age >18 years
- Ischemic stroke confirmed by clinical and imaging criteria
- Hemiparesis including reduced upper-extremity function
- Location of stroke either cortically involving middle cerebral artery or the anterior cerebral artery circulation or subcortical (involving thalamus, basal ganglia).
- NIHSS score >2 and <8
- Modified Rankin Scale (mRS) ≤ 3
- Index of stroke within 4 weeks of inclusion
- Signed informed consent
Patients - Exclusion Criteria:
- >50% stenosis of extra- or intracranial artery as well as vascular malformations or aneurisms detected by brain CT-angiography.
- Exclusively ischemic stroke in spine, pons, brainstem, medulla or cerebellum.
- History of seizures, epilepsy, anxiety, dementia alcohol- or drug abuse.
- Prior serious head injury or neurosurgery
- Frequent severe headaches or migraine.
- Pregnancy or breastfeeding
- Current use of neuro-receptor/transmitter modulating medication, or medication interfering with seizure threshold (such as antiepileptic medication, some antidepressants, anxiety medication, antihistamines, stimulant drugs for attention deficit hyperactivity disorder).
- Pacemaker, implantable cardiac device unit (ICD-unit), metal fragments or other materials implanted not compatible with MRI (see appendix B).
- Claustrophobia
- Prior adverse effect to TDCS or Transcranial Magnetic Stimulation.
- Not able to provide informed consent.
- Terminally ill or short life expectancy.
Healthy controls - Inclusion criteria:
- Age between >18 years (matched to patients)
- Sex and age matched to patients
- Able bodied
- Have the ability to comply with all requirements of the study protocol, as determined by the investigator
- No history of stroke or dementia
- Eligible for MRI and TMS
Healthy controls - Exclusion Criteria:
- History of neurologic disease
- History of cerebral haemorrhage or brain damage
- Pregnancy
- Pacemaker or other implanted electronic devices
- Claustrophobia
- Psychiatric disorder
- Epilepsy or close relatives suffering from epilepsy
- Migraine
- Any contraindication to MRI or TMS
Sites / Locations
- Copenhagen University Department of Nutrition and ExerciseRecruiting
- Department of Neurology, Herlev Gentofte HospitalRecruiting
- Danish Research Centre for Magnetic ResonanceRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active Transcranial Direct Current Stimulation
Sham stimulation
Arm Description
Anodal TDCS 1mV for 2x 20 minutes.
2x 20 minutes of sham stimulation (30 sec ramp up, followed by current of 0 for 18.5 minutes followed by 30 sec ramp down).
Outcomes
Primary Outcome Measures
Upper-extremity motor outcome
Difference in change in Upper-extremity Fugl-Meyer Assessment (UE-FMA) score. Range 0-66.
Secondary Outcome Measures
Upper-extremity function
Difference in change in Action Reach Arm Test (ARAT) score. Range 0-57. High scores mean a better outcome.
Stroke severity
Difference in change in National Health Institutes Stroke Scale (NIHSS). Range 0-42. High scores mean a better outcome.
Stroke disability
Difference in change in Modified Rankin Scale (mRS). Range 0-6. Lower scores mean a better outcome.
ADL performance
Difference in change in Bartel's 20-item Index (BI-20). Range 0-100. Higher scores mean better outcome.
Gait speed
Difference in change in 10 Meter Walk Test (10MWT) in minutes:sec.
Physical Activity
Difference in change in Physical Activity Scale 2.0 (PAS2). The answers will be translated into a Metabolic Equivalent of Task (MET)-score. The higher MET-score the higher level of activity.
Montreal Cognitive Assessment
Difference in change in Montreal Cognitive Assessment (MoCA) score. Score range 0-30. Higher scores mean a better outcome.
Symbol Digit Modalities Test
Difference in change in Symbol Digit Modalities Test (SDMT) score. Score range 0-110. Higher scores mean a better outcome.
Health-related quality of life
Difference in change in EQ-5D-5L score. Range 1 to 20, a high score means low health-related quality of life. Includes a 0-100 visual analogue scale for overall percieved quality of life.
Becks Depression Inventory (BDI)
Difference in change in BDI-II score. Score range 0-63. Higher score means increased risk of depression.
Fatigue Severity Scale (FSS)
Difference in change in FSS score. Score range 0-7. Higher score means increased fatigue severity.
WHO-5 Well-Beeing Index
Difference in change in WHO-5 score. Score range 0-100. Higher score means better quality of life.
Biomarker of inflammation and exercise
Difference in change in serum level Cathepsin-B (unit mikro gram/L)
MRI - Cerebral bloodflow
Change in cerebral blood flow measured with arterial spin labeling (ASL) during rest
fMRI - Effective connectivity
Change in activation patterns measured with blood-oxygen-level dependent (BOLD) during both single and bimanual task.
fMRI - Interhemispheric inhibition
Change in activation pattern measured by blood-oxygen-level dependent (BOLD) during both single and bimanual task.
fMRI - Laterality Index
Change in activation pattern for hemispheric dominance measured by the ratio of active fMRI voxels in each hemisphere.
MRI - Corticospinal integrity
Change in corticospinal integrity measured by diffusion MRI.
MRI - Infarct lesion load
Difference in change in size of infarct lesion meaured by structural MRI.
Full Information
NCT ID
NCT05355831
First Posted
April 26, 2022
Last Updated
December 13, 2022
Sponsor
Christina Kruuse
Collaborators
Danish Research Centre for Magnetic Resonance, The Novo Nordic Foundation, University of Copenhagen, Lundbeck Foundation
1. Study Identification
Unique Protocol Identification Number
NCT05355831
Brief Title
Patient-tailored Transcranial Direct Current Stimulation to Improve Stroke Rehabilitation
Acronym
PRACTISE
Official Title
Patient-tailored Transcranial Direct Current Stimulation to Improve Stroke Rehabilitation
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 28, 2022 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christina Kruuse
Collaborators
Danish Research Centre for Magnetic Resonance, The Novo Nordic Foundation, University of Copenhagen, Lundbeck Foundation
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
In a double-blinded sham-controlled study the effect of patient-tailored transcranial direct current stimulation during rehabilitation training will be examined.
Detailed Description
Approximately two thirds of stroke patients have reduced motor function which have a large impact on both activities of daily living and quality of life. Only 12-34% achieve full motor recovery.
There is a growing interest in using non-invasive brain stimulation (NIBS) techniques to supplement neurorehabilitation. NIBS can modulate cortical excitability and is a powerful tool for motor rehabilitation post-stroke. Application Transcranial Direct Current Stimulation (TDCS) is currently emerging as a tool used in neurorehabilitaiton. Prior studies have shown that TDCS-stimulation prior to physical training may significantly improve of motor function post-stroke. However, up to 50% of the participants recieving active TDCS show no response to stimulation.
A one-size-fits-all approach to TDCS in stroke rehabilitation may not be optimal and a more precise and individualized targeting is warranted to stimulate functionally relevant areas.
In this study TDCS will be personalized for stroke patients with upper-extremity paresis using individual functional and structural Magnetic Resonance Imaging (MRI) and an electric field modelling pipeline developed at Danish Research Centre for Magnetic Resonance (DRMCR). Based on these measures the electric current induced by TDCS will individually target the area with residual neural activity during movement. The effect of personalized TDCS will be assessed by clinical measures of motor improvement. Sub-studies furthermore assess if the functional reorganization of motor networks is affected by personalized TDCS by application of functional magnetic resonance (fMRI) and.
The study will have 3 phases:
Personalization: The stimulation profile of each patient will be individualized using structural MRI a pipeline for simulation based on MRI (SimNIBS) to make individual anatomical head models in order to estimate the best montage and current dosage. Further, task-based fMRI will be used to estimate residual motor activity location. The target current is set in the area displaying the highest residual motor activity in sensorimotor areas.
Intervention: Four weeks upper extremity training program of specialized supervised physiotherapeutic training 3 times per week. Each training session consists of 2x 20 minutes of training with concurrent personalized TDCS stimulation or montage of equipment but no stimulation (sham). Each bloc of 20 minutes training is separated by a small break of 5-10 minutes. Both patient, therapist and investigator will be blinded to the stimulation mode (activ TDCS or sham)
Follow-up: Immediately after the 4 weeks of intervention and 12 weeks after intervention has ended, follow-up with clinical examination and brain MRI will be done.
Ad baseline Transcranial Magnetic Stimulation (TMS) will be done as well to assess corticospinal integrity as well as estimation of intracortical inhibition.
Hypothesis:
The main hypothesis is that personalized ipsi-lesional anodal TDCS during specialized individualized arm-training will lead to significantly greater improvements in upper-extremity motor function compared to sham.
Substudy with healthy controls:
A cohort of 20 healthy age- and sex matched controls will be recruited for one session of MRI and TMS identical to the procedure of the patients at baseline as well as the same questionnaires (Protocol amendment approved by the local Ethics Committee the 10th October 2022).
These data will be analyzed in a substudy for normative comparison between the stroke patients and healthy age- and sex-matched controls.
Hypothesis - Healthy Controls:
Stroke patients will exhibit a higher laterality index measured by fMRI and a stronger degree of interhemispheric inhibition at baseline compared to healthy controls measued by task-related fMRI and by TMS iSP and SICI.
The degree of interhemispheric inhibition in stroke patients will normalize during recovery and be similar to normal controls at the last follow-up after 12 weeks.
Further, the degree of normalization of the interhemispheric inhibition in stroke patients will be proportional to degree of improvement of the upper-extremity measured by UE-FMA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Upper Extremity Hemiparesis
Keywords
non-invasive brain stimulation, transcranial direct current stimulation, effective connectivity, functional connectivity, Fugl-Meyer Assessment, Functional Magnetic Resonance Imaging
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Transcranial Direct Current Stimulation
Arm Type
Active Comparator
Arm Description
Anodal TDCS 1mV for 2x 20 minutes.
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
2x 20 minutes of sham stimulation (30 sec ramp up, followed by current of 0 for 18.5 minutes followed by 30 sec ramp down).
Intervention Type
Device
Intervention Name(s)
Active Transcranial Direct Current Stimulation
Intervention Description
See arm/group description
Intervention Type
Device
Intervention Name(s)
Sham stimulation
Intervention Description
See arm/group description
Primary Outcome Measure Information:
Title
Upper-extremity motor outcome
Description
Difference in change in Upper-extremity Fugl-Meyer Assessment (UE-FMA) score. Range 0-66.
Time Frame
From baseline to four months
Secondary Outcome Measure Information:
Title
Upper-extremity function
Description
Difference in change in Action Reach Arm Test (ARAT) score. Range 0-57. High scores mean a better outcome.
Time Frame
From baseline to four months
Title
Stroke severity
Description
Difference in change in National Health Institutes Stroke Scale (NIHSS). Range 0-42. High scores mean a better outcome.
Time Frame
From baseline to four months
Title
Stroke disability
Description
Difference in change in Modified Rankin Scale (mRS). Range 0-6. Lower scores mean a better outcome.
Time Frame
From baseline to four months
Title
ADL performance
Description
Difference in change in Bartel's 20-item Index (BI-20). Range 0-100. Higher scores mean better outcome.
Time Frame
From baseline to four months
Title
Gait speed
Description
Difference in change in 10 Meter Walk Test (10MWT) in minutes:sec.
Time Frame
From baseline to four months
Title
Physical Activity
Description
Difference in change in Physical Activity Scale 2.0 (PAS2). The answers will be translated into a Metabolic Equivalent of Task (MET)-score. The higher MET-score the higher level of activity.
Time Frame
From baseline to four months
Title
Montreal Cognitive Assessment
Description
Difference in change in Montreal Cognitive Assessment (MoCA) score. Score range 0-30. Higher scores mean a better outcome.
Time Frame
From baseline to four months
Title
Symbol Digit Modalities Test
Description
Difference in change in Symbol Digit Modalities Test (SDMT) score. Score range 0-110. Higher scores mean a better outcome.
Time Frame
From baseline to four months
Title
Health-related quality of life
Description
Difference in change in EQ-5D-5L score. Range 1 to 20, a high score means low health-related quality of life. Includes a 0-100 visual analogue scale for overall percieved quality of life.
Time Frame
From baseline to four months
Title
Becks Depression Inventory (BDI)
Description
Difference in change in BDI-II score. Score range 0-63. Higher score means increased risk of depression.
Time Frame
From baseline to four months
Title
Fatigue Severity Scale (FSS)
Description
Difference in change in FSS score. Score range 0-7. Higher score means increased fatigue severity.
Time Frame
From baseline to four months
Title
WHO-5 Well-Beeing Index
Description
Difference in change in WHO-5 score. Score range 0-100. Higher score means better quality of life.
Time Frame
From baseline to four months
Title
Biomarker of inflammation and exercise
Description
Difference in change in serum level Cathepsin-B (unit mikro gram/L)
Time Frame
From baseline to four months
Title
MRI - Cerebral bloodflow
Description
Change in cerebral blood flow measured with arterial spin labeling (ASL) during rest
Time Frame
From baseline to four months
Title
fMRI - Effective connectivity
Description
Change in activation patterns measured with blood-oxygen-level dependent (BOLD) during both single and bimanual task.
Time Frame
From baseline to four months
Title
fMRI - Interhemispheric inhibition
Description
Change in activation pattern measured by blood-oxygen-level dependent (BOLD) during both single and bimanual task.
Time Frame
From baseline to four months
Title
fMRI - Laterality Index
Description
Change in activation pattern for hemispheric dominance measured by the ratio of active fMRI voxels in each hemisphere.
Time Frame
From baseline to four months
Title
MRI - Corticospinal integrity
Description
Change in corticospinal integrity measured by diffusion MRI.
Time Frame
From baseline to four months
Title
MRI - Infarct lesion load
Description
Difference in change in size of infarct lesion meaured by structural MRI.
Time Frame
From baseline to four months
Other Pre-specified Outcome Measures:
Title
Brain Derived Neutrotrophic Factor (BDNF) genetic polymorphism
Description
Determination of BDNF genetic variant - either Val66Met variant or wildtype.
Time Frame
Baseline
Title
Feasibility of intervention
Description
Completion of intervention in the active vs. control group
Time Frame
From baseline to four months
Title
TMS - motor evoked potential
Description
Determination of existence of a MEP-response by TMS as an indicator of cortico-spinal tract integrity. Prognostic marker of motor recovery.
Time Frame
Baseline
Title
TMS - Ipsilateral silent period (iSP)
Description
Determination of degree of interhemispheric inhibition unaffected vs. affected hemisphere
Time Frame
Baseline
Title
TMS - Short latency intracortical inhibition (SICI)
Description
Determination of degree of interhemispheric inhibition unaffected vs. affected hemisphere
Time Frame
Baseline
Title
TMS - cortico-motor conduction time (CMCT)
Description
Determination of conduction time from stimulation of cortical neurons to response measured in a peripheral muscle (FDI)
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Patients - Inclusion Criteria:
Age >18 years
Ischemic stroke confirmed by clinical and imaging criteria
Hemiparesis including reduced upper-extremity function
Location of stroke either cortically involving middle cerebral artery or the anterior cerebral artery circulation or subcortical (involving thalamus, basal ganglia).
NIHSS score >2 and <8
Modified Rankin Scale (mRS) ≤ 3
Index of stroke within 4 weeks of inclusion
Signed informed consent
Patients - Exclusion Criteria:
>50% stenosis of extra- or intracranial artery as well as vascular malformations or aneurisms detected by brain CT-angiography.
Exclusively ischemic stroke in spine, pons, brainstem, medulla or cerebellum.
History of seizures, epilepsy, anxiety, dementia alcohol- or drug abuse.
Prior serious head injury or neurosurgery
Frequent severe headaches or migraine.
Pregnancy or breastfeeding
Current use of neuro-receptor/transmitter modulating medication, or medication interfering with seizure threshold (such as antiepileptic medication, some antidepressants, anxiety medication, antihistamines, stimulant drugs for attention deficit hyperactivity disorder).
Pacemaker, implantable cardiac device unit (ICD-unit), metal fragments or other materials implanted not compatible with MRI (see appendix B).
Claustrophobia
Prior adverse effect to TDCS or Transcranial Magnetic Stimulation.
Not able to provide informed consent.
Terminally ill or short life expectancy.
Healthy controls - Inclusion criteria:
Age between >18 years (matched to patients)
Sex and age matched to patients
Able bodied
Have the ability to comply with all requirements of the study protocol, as determined by the investigator
No history of stroke or dementia
Eligible for MRI and TMS
Healthy controls - Exclusion Criteria:
History of neurologic disease
History of cerebral haemorrhage or brain damage
Pregnancy
Pacemaker or other implanted electronic devices
Claustrophobia
Psychiatric disorder
Epilepsy or close relatives suffering from epilepsy
Migraine
Any contraindication to MRI or TMS
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina Krusse, MD, Prof
Phone
+4538681233
Email
christina.kruuse@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Mia Kolmos, MD
Phone
+4538681375
Email
mia.kolmos@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina Kruuse, MD, Prof
Organizational Affiliation
Herlev Gentofte Hospital, Department of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Copenhagen University Department of Nutrition and Exercise
City
Copenhagen
ZIP/Postal Code
2200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anke Karabanov, MSc, PhD
Phone
+4535328039
Email
anke@nexs.ku.dk
First Name & Middle Initial & Last Name & Degree
Anke Karabanov, MSc, PhD
Facility Name
Department of Neurology, Herlev Gentofte Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Kruuse, MD, Prof
Phone
+4538681233
First Name & Middle Initial & Last Name & Degree
Mia Kolmos, MD
Phone
+4538681375
Email
mia.kolmos@regionh.dk
First Name & Middle Initial & Last Name & Degree
Christina Kruuse, MD, Prof
First Name & Middle Initial & Last Name & Degree
Mia Kolmos, MD
Facility Name
Danish Research Centre for Magnetic Resonance
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hartwig R Siebner, MD, Prof
Phone
+4538626541
Email
hartwig.roman.siebner@regionh.dk
First Name & Middle Initial & Last Name & Degree
Axel Thielscher, MSc, Prof
Phone
+4538623326
Email
axelt@drcmr.dk
First Name & Middle Initial & Last Name & Degree
Hartwig R Siebner, MD, Prof
First Name & Middle Initial & Last Name & Degree
Axel Thielscher, MSc, Prof
First Name & Middle Initial & Last Name & Degree
Marie Louise Liu, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD can be accessed upon reasonable request and after evaluation from the investigator.
Learn more about this trial
Patient-tailored Transcranial Direct Current Stimulation to Improve Stroke Rehabilitation
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