Transcranial Direct Current Stimulation for Post-stroke Gait Rehab
Phase: NA
Conditions: Stroke, Gait Impairment
Sponsor: VA Office of Research and Development

Transcranial Direct Current 
Stimulation for Post-stroke Gait 
Rehab  
NCT03666533
July 13, 2023

Simultaneous transcranial direct current stimulation and gait training for chronic stroke 
NCT 03666533 
 
Abbreviated Protocol (from last IRB approved version- 07/2023)   
 
SPECIFIC AIMS Gait deficits following stroke are prevalent and frequently persistent after 
stroke.  Current rehabilitation methods fail to restore normal gait for many stroke survivors.  
Those who have persistent gait deficits following stroke even after intensive rehabilitation efforts 
tend to be more dependent on caregivers for assistance with ADLs, demonstrate limitations in 
household and/or community ambulation, are at higher risk for falls, and report poor quality of 
life (QOL).  One promising treatment method that warrants further investigation is transcranial 
Direct Current Stimulation (tDCS), a form of non-invasive brain stimulation (NIBS).  If found to 
be effective, tDCS is readily deployable into the neurorehabilitation clinical setting because of its 
safety, ease of set-up and ability to be paired with other established and effective gait 
rehabilitation methods. The purpose of this current study is to develop treatment methods that 
improve gait for those with persistent deficits following stroke. In the proposed study, we will 
compare the response to active tDCS+gait training versus sham tDCS +gait training. Gait 
training will be provided within a virtual reality (VR) gait training system and overground and will 
ensure a consistent, repeated motor learning-based pattern of practice.  AIM 1:  Determine 
whether the combination of simultaneous tDCS and gait training produces superior 
improvement in gait performance than gait training alone. Hypothesis 1:  There is an additive 
advantage in combining tDCS and gait training in improving gait performance in chronic stroke 
survivors. AIM 2:  Characterize the neuroplastic brain changes in response to bihemispheric 
tDCS combined with gait training. Hypothesis 2:  The combination of gait training and tDCS 
results in a greater increase in corticospinal excitability and strengthened functional connectivity 
compared with gait training alone. AIM 3:  Identify factors that predict gait improvement in 
response to tDCS with gait training. Hypothesis 3a: Greater gait improvement in response to 
bihemispheric tDCS with gait training is related to the following combination of baseline factors 
1) corticospinal tract (CST) lesion load; 2) greater motor abilities of the affected lower extremity; 
3) greater corticospinal excitability; 4) greater functional connectivity; 5) higher integrity of the 
stroke-affected corticospinal tract; and, 6) lesion type (cortical, subcortical, brain stem).  
Hypothesis 3b: Greater gait improvement in response to bihemispheric tDCS is dependent on 
the tDCS-induced electrical current density at the targeted cortical areas in the primary motor 
cortex for lower extremities. 
 
Study design overview This study is testing the efficacy of utilizing tDCS during gait training 
for individuals with chronic stroke (>6 mo post-stroke) who demonstrate an abnormal gait 
pattern. This is a randomized controlled multi-session study to test the potential benefit of 
combining tDCS and gait training for individuals with chronic gait deficits after stroke.  The key 
exclusion criteria will be more than one stroke, contraindications for transcranial magnetic 
stimulation, and presence of implanted medical devices such as cardiac pacemaker or vagus 
nerve stimulator.  .  
Study intervention Subjects participated in 10 treatment sessions, a baseline testing  (includes 
MRI), a mid-treatment testing session, a testing session after the 10th treatment session 
(includes MRI) and a 6-week follow-up testing visit. Clinical outcome measures were collected 
by a trained study staff who is not involved in therapy and blinded to group allocation. Subjects 
will be randomly allocated to either Treatment Group    1) active tDCS+gait training or 
Treatment Group 2) sham tDCS+gait training. Each VR gait training session lasted 30 minutes 
and tDCS will be “on” for the first 15 minutes while the subject simultaneously participates in gait 
training with guidance of a study physical therapist. Immediately after VR+tDCS training, 

subjects participated in 30 minutes of overground training guided by a physical therapist.  Home 
exercises were assigned to be completed on non-training days and reinforced in-person therapy 
training.  Both, the subject and the study staff who is delivering therapy were blinded to group 
allocation.  
Aims 1 and 2 analysis: We directly compare pre to post changes for gait speed and paretic 
single limb stance duration between the two groups. Similarly, secondary outcome measure 
changes are being compared between the study groups. We compare trajectories of changes in 
primary and secondary outcome measures afforded by longitudinal measurement through the 
course of study participation, using mixed models and the analysis of Treatment Group by time 
interaction effects. Time is considered as a categorical variable as well as modeled with random 
slope parameters. Two-sample comparisons of change values are conducted with t-tests or 
nonparametric methods such as Mann-Whitney U tests.  
Aim3 analysis: We correlate change in clinical gait performance measures in response to 
intervention with baseline variables describing the structural integrity of the corticospinal tracts, 
functional brain connectivity and lower limb motor abilities.  We also explore regression 
analyses where changes in gait measures is modeled as a dependent variable, and include 
predictors such as baseline TMS measures (MEP-rc), DTI measures, functional connectivity, 
motor ability measure and electrical field estimate values.  
Inclusion and Exclusion Criteria 
Inclusion criteria 
• 
Medically stable and at least 6 months after first ever stroke 
• 
Cognition sufficiently intact to give valid informed consent 
• 
Ability to follow two stage commands. 
• 
Sufficient endurance to participate in the study. 
• 
Age >18  
• 
Observable stance gait deficit while walking on level surface. 
Exclusion Criteria 
• 
Acute or progressive cardiac, renal, respiratory, neurological disorders or malignancy.  
• 
Any psychiatric diagnosis or active psychological condition 
• 
More than one ischemic stroke or stroke affecting both sides 
• 
Lower motor neuron damage or radiculopathy 
• 
No observable gait deficit during ambulation  
• 
Presence of implanted medical devices such as cardiac pacemakers and defibrillators, 
intrathecal drug delivery pumps, or spinal cord, vagus nerve or similar stimulators, or 
cochlear implants 
• 
Presence of metallic hardware in close contact with the TMS coil such as intracranial 
implants, aneurysm clips, plates, electrodes 
• 
Past history of seizures or unexplained loss of consciousness 
• 
Family history of medication refractory epilepsy 
• 
History of substance abuse within the last 6 months 

• 
Chronic sleep deprivation, ongoing untreated sleep disorder 
• 
Pregnancy or pregnancy planning during the study period 
• 
Inability to understand English. 
• 
Activity tolerance insufficient to complete  VR treadmill training.