TDCS to Improve Post-Stroke Cognitive Impairment

NCT ID: NCT05195398

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2027-08-31

Brief 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). 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.

Conditions

Stroke; Stroke Sequelae; Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Anodal transcranial Direct Current Stimulation (A-tDCS)

Intervention Type: DEVICE

Participants randomized to tDCS will undergo 5 weeks of A-tDCS + CCT.

Sham Intervention

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).

Group Type: ACTIVE_COMPARATOR

Sham Intervention

Intervention Type: DEVICE

Participants randomized to sham-intervention will undergo 5 weeks of sham + CCT.

Interventions

Anodal transcranial Direct Current Stimulation (A-tDCS)

Participants randomized to tDCS will undergo 5 weeks of A-tDCS + CCT.

Intervention Type: DEVICE

Sham Intervention

Participants randomized to sham-intervention will undergo 5 weeks of sham + CCT.

Intervention Type: DEVICE

Other Intervention Names

Computerized Cognitive Therapy (CCT); Computerized Cognitive Therapy (CCT)

Eligibility Criteria

Inclusion Criteria

1. Adults (≥18 years) presenting with neurological symptoms due to acute ischemic stroke (symptom onset within the week prior to admission).

2. Evidence on brain MRI of acute ischemic stroke (imaging negative strokes and TIAs will be excluded).

3. Native English speaker (by self-report) prior to stroke.

4. NIHSS <8 at initial follow-up visit (approximately 30 days post-stroke).

5. mRS 0-2 at initial follow-up visit.

Exclusion Criteria

1. Primary intracerebral hemorrhage- as evidenced by blood on head CT or MRI.

2. Presence of proximal large vessel occlusion.

3. Cortical exam findings including aphasia or neglect.

4. Prior report or history of dementia or undertreated psychiatric illness.

5. Uncorrected hearing or visual loss.

6. Inability to attend treatment or follow-up sessions.

7. Inability to travel to College Park (UMD) for MEG recording sessions.

8. 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).

9. Claustrophobia, obesity, and/or any other reason leading to difficulty staying in the MEG machine for up to 1 hour.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, College Park

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth B Marsh, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Elisabeth B Marsh, MD

Role: CONTACT

ebmarsh@jhmi.edu

410-550-8703

Facility Contacts

Eliabeth B Marsh, MD

Role: primary

ebmarsh@jhmi.edu

410-550-8703

Rafael H Llinas, MD

Role: backup

rllinas@jhmi.edu

4105501042

References

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.

Reference Type: BACKGROUND

PMID: 33318200 (View on PubMed)

Marsh 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.

Reference Type: BACKGROUND

PMID: 29306185 (View on PubMed)

Sharma 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.

Reference Type: BACKGROUND

PMID: 33424761 (View on PubMed)

Related Links

http://www.marshlab.org

Marsh Lab website

Other Identifiers

IRB00315010

Identifier Type: -

Identifier Source: org_study_id