Brain State-Dependent PCMS for Stroke Recovery

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas at Austin

Must not be taking: Antipsychotics, Benzodiazepines, Stimulants, others

Disqualifiers: Neurological disease, Metal in body, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help people regain hand function after a stroke. It combines brain and nerve stimulation, known as Brain State-dependent Paired Corticomotoneuronal Stimulation (PCMS), to strengthen pathways controlling hand movements. The study will determine if timing the stimulation during specific brain states enhances recovery more than random stimulation. Individuals who had a stroke over six months ago and still struggle with hand use might be suitable candidates. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to pioneering stroke recovery advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that act on the central nervous system, except for selective serotonin reuptake inhibitors (SSRIs), at least 3 months before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Brain State-dependent PCMS, a method combining brain and nerve stimulation, is generally well-tolerated. Some studies have demonstrated positive effects on movement abilities after strokes. For example, one study found that this technique improved movement and reduced difficulties in moving. Another study noted an increase in how well the brain communicates with muscles after treatment.

While these studies provide encouraging results, they are not very large. However, they suggest that the treatment does not cause major unwanted effects. As this trial is in its early stages, researchers are still collecting more data on safety. The findings so far are promising and suggest the treatment is safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Brain State-Dependent Paired Corticomotoneuronal Stimulation (PCMS) for stroke recovery because it takes a novel approach by synchronizing stimulation with specific brain activity patterns. Unlike traditional rehabilitation methods, which often involve physical therapy and medication, this technique aims to enhance the brain's natural ability to rewire itself by targeting optimal moments of corticospinal transmission. This precision could potentially lead to faster and more effective recovery of motor functions in stroke patients. Additionally, the trial investigates the impact of delivering PCMS during random brain states as an active comparator, offering insights into how timing can influence treatment outcomes.

What evidence suggests that this trial's treatments could be effective for stroke recovery?

This trial will compare two approaches to brain stimulation for stroke recovery. One group of participants will receive Brain State-dependent Paired Corticomotoneuronal Stimulation (PCMS) during brain states reflecting strong corticospinal transmission. Another group will receive PCMS during random brain states. Research has shown that this special type of brain stimulation can aid stroke patients in better recovery. In one study, patients who received this treatment improved their hand movement more than those who did not. This method activates the brain and nerves together to strengthen the pathways that control movement, similar to how highways carry traffic. By timing the stimulation to match certain brain activities, these pathways become stronger. Early results are promising for helping stroke patients improve their hand function by making these pathways work more efficiently. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals who have had a stroke at least 6 months ago and now struggle with hand function due to upper extremity hemiparesis. They must be mentally fit (with a Mini Mental State Exam score over 24), willing to participate, able to consent, and have some movement in their affected arm but not full recovery (Fugl-Meyer score under 66).

Inclusion Criteria

I had a stroke more than 6 months ago.

You scored higher than 24 on the Mini Mental State Exam.

I have weakness in one of my arms.

Exclusion Criteria

Your score on a mental exam is 24 or lower.

You have medical reasons that make it unsafe for you to receive transcranial magnetic stimulation or peripheral nerve stimulation.

My brain does not respond normally to a specific type of brain scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined brain and nerve stimulation during specific time windows to enhance hand function

4 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain State-dependent Paired Corticomotoneuronal Stimulation (PCMS)
• Phase-dependent Paired Corticomotoneuronal Stimulation (PCMS)

Trial Overview

The study tests whether delivering paired corticomotoneuronal stimulation (PCMS) during specific brain states improves hand function after stroke compared to random timing of PCMS. It aims to strengthen the neural pathways that control the hand by using combined brain and nerve stimulation.

How Is the Trial Designed?

Group I: PCMS during brain states reflecting strong corticospinal transmission Experimental Treatment 1 Intervention

Group II: PCMS during random brain states Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Published Research Related to This Trial

The TMS Synchronized Exoskeleton Feedback (TSEF) platform, which combines real-time feedback from exoskeleton movements and brain stimulation, showed promising results in enhancing cortical excitability in stroke patients, with a significant increase in Motor Evoked Potential and improvement in clinical scales after 20 sessions.

In a proof-of-concept study involving three patients, the TSEF platform demonstrated clinical gains that were not observed in a control group receiving standard physiotherapy, suggesting that personalized brain stimulation may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study. Singh, N., Saini, M., Kumar, N., et al.[2023]

New brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex of stroke patients, potentially improving motor function.

Activity-dependent stimulation, which tailors brain stimulation to the patient's neural or muscular activity, may offer even better outcomes compared to traditional neurorehabilitation methods, suggesting a promising direction for future stroke rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New modalities of brain stimulation for stroke rehabilitation. Edwardson, MA., Lucas, TH., Carey, JR., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11130975/

The Effectiveness of Paired Associative Stimulation on ...

Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12481022/

Promoting motor recovery after stroke using cortico-cortical ...

A promising therapeutic approach involves combining non-invasive brain stimulation (NIBS) with activity-based training to enhance neuroplasticity. NIBS are ...

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1002/ana.25375

Brain state–dependent stimulation boosts functional ...

The associative group significantly improved functional recovery with respect to the control group (median [interquartile range] LE-FM ...

4.

bmcneurol.biomedcentral.com

bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03218-2

Effects of cortico-cortical paired associative stimulation based ...

Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) ...

5.

academic.oup.com

academic.oup.com/brain/article/148/7/2361/7997945

Pathway-dependent brain stimulation responses indicate ...

These findings indicate that targeted ccPAS can effectively engage functionally relevant residual visual pathways in stroke-affected brains, ...

6.

clinicaltrial.be

clinicaltrial.be/en/details/45548?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&not_yet_recruiting=0&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Brain State-dependent PCMS in Chronic Stroke

In this study, paired corticomotoneuronal stimulation (PCMS) will be applied during specific brain states that reflect increased recruitment of ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10148448/

Effects of cortico-cortical paired associative stimulation based ...

This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0149763424004020

Investigating the effects of cortico-cortical paired ...

The study found an increase in CSE and a decrease in short interval intracortical inhibition (SICI) measured at rest after the ccPAS intervention, suggesting ...

9.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1427198/full

Brain state-dependent repetitive transcranial magnetic ...

This pilot study demonstrated that the brain oscillation-synchronized rTMS protocol produced beneficial effects on motor impairment, motor function and ...