Establishing a Prognostic Model for Stroke Recovery

NCT05332652 | Active Not Recruiting DMC

• 1 other identifier: 2019/00932
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

This main aim of the study is to investigate the changes in neurophysiological features after stroke, and its association with upper limb motor recovery, so as to establish a prognostic model for upper limb motor recovery after stroke. The investigators hypothesize that a combination of neurophysiological features measured by transcranial magnetic stimulation (TMS), high density electroencephalography (HD-EEG), functional magnetic resonance imaging (fMRI) and Diffusion Tensor Imaging (DTI) might be used as biomarkers to predict upper limb motor outcomes after stroke. The investigators also hypothesize that non-invasive brain stimulation strategies such as tDCS will more effectively improve motor outcomes as an adjunct to therapy, if tailored according to patient's predicted pattern of neural reorganization.

Conditions

Stroke, Acute

Keywords

stroke; motor recovery; prognostic model; transcranial magnetic stimulation; transcranial direct current stimulation; neuromodulation

Outcome Measures

Primary Outcomes (6)

• Change of cortical excitability using Transcranial Magnetic Stimulation (TMS)

  measures of cortical excitability for those without TMS contraindications

  Change of the cortical excitability within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

• Change of neural excitability using Magnetic resonance imaging (MRI) scan

  Participants will go through one of the following image acquisition procedures 1) a functional MRI scans for brain activity together with motor task. 2) a 3D MPRAGE sequence for brain structure. 3) an advanced multishell high-resolution diffusion MRI for characterizing brain microstructure and extracellular space. 4) a FLAIR scan to measure white matter hyperintensity. Both functional and anatomical image acquisition will be undertaken using but not limited to gradient echo EPI sequence or its modified version.

  Change of the neural excitability within 4 weeks, at 3 months, 6 months after stroke onset

• Change of neural excitability using electroencephalogram (EEG)

  High density EEG (electroencephalogram) evaluation of the electrical activity of the brain

  Change of the neural excitability within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

• Change of the upper extremity motor function using Fugl-Meyer scale

  Upper limb function, Minimum score 0, Maximum score 66, the higher the score the better the upper limb function.

  Change of the upper extremity motor function within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

• Change of upper extremity performance (coordination, dexterity and functioning) using Action Research Arm Test

  Upper limb function, Minimum score 0, Maximum score 57, the higher the score the better the upper limb function.

  Change of upper extremity performance within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

• Change of muscle spasticity using Modified Ashworth scale for spasticity (MAS)

  Upper limb function, 6 point scale, Scores range from 0 to 4 (namely 0, 1, 1+, 2, 3 and 4), where lower scores represent normal muscle tone and higher scores represent spasticity or increased resistance to passive movement.

  Change of muscle spasticity within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

Secondary Outcomes (1)

• Change of cognitive function using cognitive test

  Change of cognitive function within 4 weeks, at 3 months, 6 months and 1 year after stroke onset

Study Arms (4)

Anodal tDCS stimulation to the ipsilesional M1

EXPERIMENTAL

Participant will receive 1 mA anodal tDCS stimulation to the ipsilesional M1 of cortical representation of the affected upper limb. Cathode will be used as reference electrode and placed over the supraorbital area contralateral to the anode. tDCS stimulation will be conducted daily for 20 sessions in consecutive days in the 4th month after stroke, with each session lasting for 20 minutes and combined with online occupational therapy training.

Device: trancranial magnetic stimulation

Anodal tDCS to the contralesional premotor cortex

EXPERIMENTAL

Participant will receive 1mA anodal tDCS to the contralesional premotor cortex. Cathode will be used as reference electrode and placed over the supraorbital area contralateral to the anode. tDCS stimulation will be conducted daily for 20 sessions in consecutive days in the 4th month after stroke, with each session lasting for 20 minutes and combined with online occupational therapy training.

Device: trancranial magnetic stimulation

Sham tDCS

SHAM COMPARATOR

Participant will receive sham tDCS stimulation with anode placed over the scalp area corresponding to ipsilesional M1. Cathode will be used as reference electrode and placed over the supraorbital area contralateral to the anode. tDCS stimulation will be conducted daily for 20 sessions in consecutive days in the 4th month after stroke, with each session lasting for 20 minutes and combined with online occupational therapy training.

Device: trancranial magnetic stimulation

Control group

NO INTERVENTION

Subjects who fulfill the inclusion criteria of Study 2 but refuse tDCS stimulation.

Interventions

trancranial magnetic stimulation DEVICE

A trained research staff or physician will perform tDCS to the subject. Direct current will be delivered by a battery-operated, constant current stimulator, through 2 rubber electrodes embedded in a pair of saline-soaked sponge bag. Stimulation intensity will be ramped up to 1 mA over 30 seconds and maintain at 1 mA for 20 minutes, and then ramped down to 0 mA over 30 seconds.

Anodal tDCS stimulation to the ipsilesional M1; Anodal tDCS to the contralesional premotor cortex; Sham tDCS

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old;
• First ever stroke less than 6 weeks;
• Moderate to severe upper limb impairment with Manual Muscle Testing (MMT) score on shoulder abduction plus finger extension (SAFE) \<5 within the first week post-stroke.
• Age 21-80 years old;
• No known medical history.

You may not qualify if:

• Pregnancy;
• Any metal implants inside the body that are contraindications of MRI scan;
• cardiac pacemakers;
• History of epilepsy;
• Sensorimotor disturbance due to other causes other than stroke;
• Claustrophobia;
• Uncontrolled medical conditions including hypertension, diabetes mellitus and unstable angina;
• Major depression and a history of psychotic disorders;
• Terminal diagnosis with life expectancy \<=1 year.
• Pregnancy;
• Any metal implants inside the body that are contraindications of MRI scan;
• cardiac pacemakers;
• Claustrophobia.

Sponsors & Collaborators

• National University of Singapore: collaborator
• Nanyang Technological University: collaborator
• National University Hospital, Singapore: lead
• Alexandra Hospital: collaborator

Study Sites (2)

Alexandra Hospital

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Effie Chew, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant in Group 1-3 will be blinded to the stimulation protocol that they will be receiving.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects from Study 1 whose ARAT score is \< = 42 at 3 months post-stroke will proceed to Study 2. Subjects who are agreeable for transcranial direct current stimulation (tDCS) will be randomized into 3 groups with 17 subjects in each group, by stratified randomization, according to the lesion location (cortical vs. subcortical), and type of stroke (haemorrhagic vs. ischemic). Subjects who refuse tDCS will be enrolled in the control group without receiving any tDCS stimulation. * Group 1 will receive 1 mA anodal tDCS stimulation to the ipsilesional M1 of cortical representation of the affected upper limb; * Group 2 to receive 1mA anodal tDCS to the contralesional premotor cortex; * Group 3 to receive sham tDCS stimulation with anode placed over the scalp area corresponding to ipsilesional M1. * Group 4: Subjects who fulfill the inclusion criteria of Study 2 but refuse tDCS stimulation.

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: April 18, 2022
• Study Start: September 1, 2020
• Primary Completion (Estimated): July 16, 2026
• Study Completion (Estimated): July 16, 2026
• Last Updated: February 20, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)