StrokeTIPSCINCT05195398
TDCS to Improve Post-Stroke Cognitive Impairment
A study testing Anodal transcranial Direct Current Stimulation (A-tDCS) in people with Stroke and Stroke Sequelae, run by Johns Hopkins University at 1 site in United States.
Trial summary
The investigators will conduct a randomized, double-blinded, sham-controlled trial of approximately 60 patients with minor stroke and post-stroke mild cognitive impairment (psMCI). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Stroke, Stroke Sequelae, Cognitive Impairment
- What is being tested?
- Anodal transcranial Direct Current Stimulation (A-tDCS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 31 Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (≥18 years) presenting with neurological symptoms due to acute ischemic stroke (symptom onset within the week prior to admission).
- Evidence on brain MRI of acute ischemic stroke (imaging negative strokes and TIAs will be excluded).
- Native English speaker (by self-report) prior to stroke.
- NIHSS <8 at initial follow-up visit (approximately 30 days post-stroke).
- mRS 0-2 at initial follow-up visit.
Who cannot join
- Primary intracerebral hemorrhage- as evidenced by blood on head CT or MRI.
- Presence of proximal large vessel occlusion.
- Cortical exam findings including aphasia or neglect.
- Prior report or history of dementia or undertreated psychiatric illness.
- Uncorrected hearing or visual loss.
- Inability to attend treatment or follow-up sessions.
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- Inability to travel to College Park (UMD) for MEG recording sessions.
- Presence of any of the following that would lead to significant artifact on MEG: cardiac pacemaker, intracranial clips, metal implants or external clips within 10mm of the head, metal implants in the eyes (unlikely given that all patients will have an MRI and criteria are similar).
- Claustrophobia, obesity, and/or any other reason leading to difficulty staying in the MEG machine for up to 1 hour.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Eliabeth B Marsh, MD, 410-550-8703, ebmarsh@jhmi.edu
Rafael H Llinas, MD, 4105501042, rllinas@jhmi.edu
About this study
The investigators will conduct a randomized, double-blinded, sham-controlled trial of approximately 60 patients with minor stroke and post-stroke mild cognitive impairment (psMCI). Participants will be individually randomized on enrollment using a random number generator to treatment with anodal tDCS + computerized cognitive treatment (CCT) versus sham + CCT (approximately 30 patients in each arm). Clinical evaluation including assessment of cognition will be performed pre- and post-intervention by individuals on the study team blinded to the participant's intervention. Participants will also undergo functional neuroimaging with magnetoencephalography (MEG) pre- and post-intervention (1, 3, and 6 months post-stroke to evaluate for initial and longer-term effects of treatment on cerebral activation patterns and functional connectivity). Neuroimaging and clinical outcomes will be assessed to determine the effect of tDCS versus sham + CCT on psMCI.
Read the detailed description
Vascular cognitive impairment, ranging from vascular mild cognitive impairment to vascular dementia, is a leading cause of progressive cognitive dysfunction second only to Alzheimer Disease. While the accumulation of ischemic infarcts or a large cortical stroke can result in permanent cognitive dysfunction, a single small stroke can also result in disabling impairment. The investigators have shown that small lesions, regardless of the location, result in acute cognitive decline. Similar to those with progressive vascular cognitive impairment, post-stroke MCI (psMCI) patients display slowed reaction times and dysfunction across multiple cognitive domains. Many significantly recover over the first 6 months. However, the heterogenous recovery and uncertainty regarding prognosis can lead to major life changes, such as early retirement or selling of homes, that substantially impact quality of life.
Magnetoencephalography (MEG) recordings in those with psMCI show temporal dispersion consistent with generalized disruption of cognitive networks during resting state, irrespective of lesion location. Evaluation of frequency spectra show bilaterally decreased beta power in the frontoparietal lobes correlating with impaired reaction times. Functional connectivity analyses at 6 months demonstrate increased inter-hemispheric connections that may explain or reflect a patient's improvement. It is currently unknown whether specific cognitive networks are involved, though based on the pattern of clinical deficits it would be reasonable to hypothesize that the frontoparietal network, responsible for executive function and higher level cognitive tasks, is disrupted to a greater extent than the limbic, responsible for emotion and memory. Neural modulation with transcranial direct current stimulation (tDCS) increases the likelihood of neural firing, strengthening connectivity by promoting long-term potentiation and facilitating task performance. As anodal tDCS only induces the firing of neurons near threshold, it follows that it is most effective and longest acting when paired with a task that engages focal activation. This is best seen in patients with aphasia undergoing speech-language therapy.
In this study, the investigators will determine the utility of A-tDCS in conjunction with computerized cognitive therapy (CCT) to treat psMCI. The investigators will recruit approximately 60 patients with subacute minor stroke and randomize the patients to A-tDCS administered over the ipsilesional frontoparietal cortex versus sham plus 15 sessions of cognitive therapy using a widely used online platform focused most on executive functioning and processing speed based on the investigators' preliminary work targeting deficits most specific to those with psMCI. The investigators hypothesize that tDCS will augment both generalized connectivity as well as the connectivity of specific networks targeted during training (most notably the frontoparietal) and that patients will show increased clinical improvement acutely after therapy that will last for months after treatment.
Along with clinical evaluation, the investigators will use MEG to evaluate cerebral activation patterns and connectivity pre- (1 month post-infarct) and post- (3 and 6 months post-infarct) intervention. The investigators will collect longitudinal MEG and clinical data through a multicenter collaboration of experts in the fields of stroke, dementia, and functional neuroimaging.
- Conditions
- Stroke, Stroke Sequelae, Cognitive Impairment
- Being tested
- Anodal transcranial Direct Current Stimulation (A-tDCS), Sham Intervention
- Medical subject headings
- Stroke, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anodal transcranial Direct Current Stimulation (A-tDCS)Device
Also called Computerized Cognitive Therapy (CCT)
Participants randomized to tDCS will undergo 5 weeks of A-tDCS + CCT.
Sham InterventionDevice
Also called Computerized Cognitive Therapy (CCT)
Participants randomized to sham-intervention will undergo 5 weeks of sham + CCT.
| Study group | Role | What they receive |
|---|---|---|
| A-tDCS | Experimental | Participants randomized to tDCS will undergo 15- 30 minute sessions over 5 weeks of A-tDCS to the ipsilesional frontoparietal cortex while participating in computerized cognitive therapy (CCT). Receives: Device: Anodal transcranial Direct Current Stimulation (A-tDCS) |
| Sham Intervention | Active comparator | Participants randomized to sham will undergo 15- 30 minute sessions over 5 weeks of a sham-intervention, also applied to the ipsilesional frontoparietal cortex, while participating in computerized cognitive therapy (CCT). Receives: Device: Sham Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognition as assessed by our Cognitive Battery
Our cognitive battery was designed to efficiently evaluate for psMCI. It combines the Montreal Cognitive Assessment, Grooved Pegboard, Hopkins Verbal Learning Test, Brief Visuospatial Memory Test, Delis-Kaplan Executive Function System, and Symbol Digit Modalities Test. T scores are averaged across tasks and calculated for the following cognitive domains: verbal memory, spatial memory, processing speed, motor speed, executive function, and global cognition.
Measured: Administered at 1, 3, and 6 month post-stroke visits
Change in Functional Connectivity as assessed by MEG
Participants will undergo an MEG evaluating global functional connectivity: 1) during resting state, and 2) during completion of a visual task. Connectivity will also be evaluated within the following specific cognitive networks: frontoparietal (executive) and limbic (memory)
Measured: Administered at 1, 3, and 6 month post-stroke visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start1 Sep 2022
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to 15- 30 minute sessions of A-tDCS + CCT versus sham-intervention + CCT over a 5 week period
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, College Park, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Elisabeth B Marsh, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05195398
- Sponsor's protocol ID
- IRB00315010
- Acronym
- TIPSCI
- Status last verified
- Aug 2026
- First submitted
- 4 Jan 2022
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Results in aggregate will be posted; however, de-identified individual participant data will be made available to other investigators and potential collaborators upon reasonable request of the PI.
Publications
Marsh EB, Brodbeck C, Llinas RH, Mallick D, Kulasingham JP, Simon JZ, Llinas RR. Poststroke acute dysexecutive syndrome, a disorder resulting from minor stroke due to disruption of network dynamics. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33578-33585. doi: 10.1073/pnas.2013231117. Epub 2020 Dec 14.
PubMed 33318200Marsh EB, Lawrence E, Hillis AE, Chen K, Gottesman RF, Llinas RH. Pre-stroke employment results in better patient-reported outcomes after minor stroke: Short title: Functional outcomes after minor stroke. Clin Neurol Neurosurg. 2018 Feb;165:38-42. doi: 10.1016/j.clineuro.2017.12.020. Epub 2017 Dec 27.
PubMed 29306185Sharma R, Mallick D, Llinas RH, Marsh EB. Early Post-stroke Cognition: In-hospital Predictors and the Association With Functional Outcome. Front Neurol. 2020 Dec 23;11:613607. doi: 10.3389/fneur.2020.613607. eCollection 2020.
PubMed 33424761
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TDCS to Improve Post-Stroke Cognitive Impairment
- ClinicalTrials.gov ID
- NCT05195398
- Acronym / sponsor ID
- TIPSCI / IRB00315010
- Conditions
- Stroke, Stroke Sequelae, Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- University of Maryland, College Park, National Institutes of Health (NIH)
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will conduct a randomized, double-blinded, sham-controlled trial of approximately 60 patients with minor stroke and post-stroke mild cognitive impairment (psMCI). Participants will be individually randomized on enrollment using a random number generator to treatment with anodal tDCS + computerized cognitive treatment (CCT) versus sham + CCT (approximately 30 patients in each arm). Clinical evaluation including assessment of cognition will be performed pre- and post-intervention by individuals on the study team blinded to the participant's intervention. Participants will also undergo functional neuroimaging with magnetoencephalography (MEG) pre- and post-intervention (1, 3, and 6 months post-stroke to evaluate for initial and longer-term effects of treatment on cerebral activation patterns and functional connectivity). Neuroimaging and clinical outcomes will be assessed to determine the effect of tDCS versus sham + CCT on psMCI.
Detailed description
Vascular cognitive impairment, ranging from vascular mild cognitive impairment to vascular dementia, is a leading cause of progressive cognitive dysfunction second only to Alzheimer Disease. While the accumulation of ischemic infarcts or a large cortical stroke can result in permanent cognitive dysfunction, a single small stroke can also result in disabling impairment. The investigators have shown that small lesions, regardless of the location, result in acute cognitive decline. Similar to those with progressive vascular cognitive impairment, post-stroke MCI (psMCI) patients display slowed reaction times and dysfunction across multiple cognitive domains. Many significantly recover over the first 6 months. However, the heterogenous recovery and uncertainty regarding prognosis can lead to major life changes, such as early retirement or selling of homes, that substantially impact quality of life.
Magnetoencephalography (MEG) recordings in those with psMCI show temporal dispersion consistent with generalized disruption of cognitive networks during resting state, irrespective of lesion location. Evaluation of frequency spectra show bilaterally decreased beta power in the frontoparietal lobes correlating with impaired reaction times. Functional connectivity analyses at 6 months demonstrate increased inter-hemispheric connections that may explain or reflect a patient's improvement. It is currently unknown whether specific cognitive networks are involved, though based on the pattern of clinical deficits it would be reasonable to hypothesize that the frontoparietal network, responsible for executive function and higher level cognitive tasks, is disrupted to a greater extent than the limbic, responsible for emotion and memory. Neural modulation with transcranial direct current stimulation (tDCS) increases the likelihood of neural firing, strengthening connectivity by promoting long-term potentiation and facilitating task performance. As anodal tDCS only induces the firing of neurons near threshold, it follows that it is most effective and longest acting when paired with a task that engages focal activation. This is best seen in patients with aphasia undergoing speech-language therapy.
In this study, the investigators will determine the utility of A-tDCS in conjunction with computerized cognitive therapy (CCT) to treat psMCI. The investigators will recruit approximately 60 patients with subacute minor stroke and randomize the patients to A-tDCS administered over the ipsilesional frontoparietal cortex versus sham plus 15 sessions of cognitive therapy using a widely used online platform focused most on executive functioning and processing speed based on the investigators' preliminary work targeting deficits most specific to those with psMCI. The investigators hypothesize that tDCS will augment both generalized connectivity as well as the connectivity of specific networks targeted during training (most notably the frontoparietal) and that patients will show increased clinical improvement acutely after therapy that will last for months after treatment.
Along with clinical evaluation, the investigators will use MEG to evaluate cerebral activation patterns and connectivity pre- (1 month post-infarct) and post- (3 and 6 months post-infarct) intervention. The investigators will collect longitudinal MEG and clinical data through a multicenter collaboration of experts in the fields of stroke, dementia, and functional neuroimaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized to 15- 30 minute sessions of A-tDCS + CCT versus sham-intervention + CCT over a 5 week period
| Arm | Type | Receives |
|---|---|---|
| A-tDCS | Experimental | Device: Anodal transcranial Direct Current Stimulation (A-tDCS)Participants randomized to tDCS will undergo 15- 30 minute sessions over 5 weeks of A-tDCS to the ipsilesional frontoparietal cortex while participating in computerized cognitive therapy (CCT). |
| Sham Intervention | Active comparator | Device: Sham InterventionParticipants randomized to sham will undergo 15- 30 minute sessions over 5 weeks of a sham-intervention, also applied to the ipsilesional frontoparietal cortex, while participating in computerized cognitive therapy (CCT). |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults (≥18 years) presenting with neurological symptoms due to acute ischemic stroke (symptom onset within the week prior to admission).
- Evidence on brain MRI of acute ischemic stroke (imaging negative strokes and TIAs will be excluded).
- Native English speaker (by self-report) prior to stroke.
- NIHSS <8 at initial follow-up visit (approximately 30 days post-stroke).
- mRS 0-2 at initial follow-up visit.
Key exclusion criteria (9 listed)
- Primary intracerebral hemorrhage- as evidenced by blood on head CT or MRI.
- Presence of proximal large vessel occlusion.
- Cortical exam findings including aphasia or neglect.
- Prior report or history of dementia or undertreated psychiatric illness.
- Uncorrected hearing or visual loss.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anodal transcranial Direct Current Stimulation (A-tDCS)Also: Computerized Cognitive Therapy (CCT)Participants randomized to tDCS will undergo 5 weeks of A-tDCS + CCT. | Device | A-tDCS |
| Sham InterventionAlso: Computerized Cognitive Therapy (CCT)Participants randomized to sham-intervention will undergo 5 weeks of sham + CCT. | Device | Sham Intervention |
Primary outcome
Change in Cognition as assessed by our Cognitive Battery
Time frame: Administered at 1, 3, and 6 month post-stroke visits
Our cognitive battery was designed to efficiently evaluate for psMCI. It combines the Montreal Cognitive Assessment, Grooved Pegboard, Hopkins Verbal Learning Test, Brief Visuospatial Memory Test, Delis-Kaplan Executive Function System, and Symbol Digit Modalities Test. T scores are averaged across tasks and calculated for the following cognitive domains: verbal memory, spatial memory, processing speed, motor speed, executive function, and global cognition.
Change in Functional Connectivity as assessed by MEG
Time frame: Administered at 1, 3, and 6 month post-stroke visits
Participants will undergo an MEG evaluating global functional connectivity: 1) during resting state, and 2) during completion of a visual task. Connectivity will also be evaluated within the following specific cognitive networks: frontoparietal (executive) and limbic (memory)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Background: PubMed 33318200Marsh EB, Brodbeck C, Llinas RH, Mallick D, Kulasingham JP, Simon JZ, Llinas RR. Poststroke acute dysexecutive syndrome, a disorder resulting from minor stroke due to disruption of network dynamics. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33578-33585. doi: 10.1073/pnas.2013231117. Epub 2020 Dec 14.
- Background: PubMed 29306185Marsh EB, Lawrence E, Hillis AE, Chen K, Gottesman RF, Llinas RH. Pre-stroke employment results in better patient-reported outcomes after minor stroke: Short title: Functional outcomes after minor stroke. Clin Neurol Neurosurg. 2018 Feb;165:38-42. doi: 10.1016/j.clineuro.2017.12.020. Epub 2017 Dec 27.
- Background: PubMed 33424761Sharma R, Mallick D, Llinas RH, Marsh EB. Early Post-stroke Cognition: In-hospital Predictors and the Association With Functional Outcome. Front Neurol. 2020 Dec 23;11:613607. doi: 10.3389/fneur.2020.613607. eCollection 2020.
- Marsh Lab websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Results in aggregate will be posted; however, de-identified individual participant data will be made available to other investigators and potential collaborators upon reasonable request of the PI.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Elisabeth B Marsh, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anodal transcranial Direct Current Stimulation (A-tDCS) in people with Stroke and Stroke Sequelae, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elisabeth B Marsh, MD (410-550-8703, ebmarsh@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognition as assessed by our Cognitive Battery (time frame: Administered at 1, 3, and 6 month post-stroke visits). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05195398, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.