Paired Associative Stimulation for Post-Stroke Recovery

Recruiting at 1 trial location

Overseen By Amit Sethi, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Utah

Must not be taking: Psychotropic, Recreational drugs

Disqualifiers: Severe aphasia, Seizure history, Others

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

Compensation: Varies

Number of Visits: 21

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a combination of brain, nerve, and hand stimulation can improve hand movement and function in people who have had a stroke. The goal is to determine if these treatments, including Task-specific Paired Cortical and Muscle Stimulation (Task-specific PCMS), can strengthen the connection between the brain and weak hand muscles. Participants will undergo various types of stimulation and practice to assess their effects. This trial suits individuals who experienced their first stroke at least six months ago and have some ability to grasp objects with their affected hand. As an unphased study, it offers a unique opportunity to contribute to innovative research that could enhance rehabilitation techniques for stroke survivors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on psychotropic medication and those using recreational drugs or stimulants like cocaine and MDMA.

What prior data suggests that this combined brain, nerve, and hand stimulation is safe for post-stroke recovery?

Research has shown that paired associative stimulation, which involves stimulating the brain and nerves, is generally well-tolerated. Studies have found that this type of stimulation can improve movement recovery in stroke patients without causing significant side effects. In one study, participants received this stimulation, and no major safety concerns emerged.

For the PCMS-rest treatment, which also involves brain and nerve stimulation without requiring specific tasks, previous research suggests it is safe. One review found that repetitive transcranial magnetic stimulation, a component of this method, is effective and safe for stroke recovery, with few side effects.

Overall, both task-specific and rest-based brain and nerve stimulations appear safe, with no major safety issues reported so far. Participants usually handle these treatments well, and they have shown promise in aiding stroke recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel approach to post-stroke recovery using Paired Associative Stimulation (PCMS). Unlike traditional therapies that often focus on physical rehabilitation exercises alone, this method combines Transcranial Magnetic Stimulation (TMS) with Peripheral Nerve Stimulation (PNS) in a task-specific manner. This dual approach aims to enhance neural plasticity, potentially leading to more effective and faster recovery by directly stimulating the brain and nerves associated with motor function. By investigating different combinations of PCMS with and without task-specific practice, researchers hope to pinpoint the most effective strategy, offering new hope for stroke survivors seeking improved recovery outcomes.

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

This trial will evaluate different approaches to paired associative stimulation for post-stroke recovery. Research has shown that Task-specific PCMS (paired corticospinal-motor neuronal stimulation), which participants in this trial may receive, can improve hand movement after a stroke. One study found that this stimulation increased the brain area controlling movement, suggesting it could aid stroke recovery. When combined with specific exercises, this stimulation has improved the recovery and function of the upper limb.

Another approach in this trial, PCMS-rest, involves similar methods. Studies on repetitive transcranial magnetic stimulation, a non-invasive brain stimulation technique, have demonstrated potential benefits for stroke recovery, suggesting that even without specific exercises, PCMS can still positively impact recovery. Overall, these treatments aim to strengthen the brain's connection to hand muscles and improve movement and function. ^{1 5 6 7 8}

Who Is on the Research Team?

Amit Sethi, PhD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who've had their first subcortical stroke at least six months ago, can grasp a ball, and have the cognitive ability to participate. It's not for those with metallic head/neck implants, severe spasticity in wrist/finger muscles, other neurological disorders besides stroke, or certain psychiatric conditions.

Inclusion Criteria

I can partially grasp a ball with my hand.

My stroke happened more than six months ago.

I have had one stroke that affected the deeper parts of my brain.

Exclusion Criteria

Bodyweight > 300 lbs due to MRI scanner dimensions (for subjects also undergoing MRI)

I struggle to stay alert or keep still.

I have a psychiatric diagnosis or am taking psychotropic medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Short-term Intervention

Participants receive three sessions of brain, hand, and nerve stimulations to assess short-term effects

3-7 days between sessions

3 visits (in-person)

Long-term Intervention

5 participants receive 18 sessions of brain, hand, and nerve stimulations over six weeks to assess long-term effects

6 weeks

18 visits (in-person)

Follow-up

Participants are monitored for changes in motor performance and corticospinal transmission after interventions

Up to 30 minutes post intervention

What Are the Treatments Tested in This Trial?

Interventions

• PCMS-rest
• Task-specific PCMS
• Task-specific sham-PCMS

Trial Overview The study tests how brain stimulation combined with nerve and hand stimulation affects hand movement after a stroke. Participants will receive either real or sham (fake) stimulations to see if this improves the connection between the brain and weak hand muscles as well as hand function.

How Is the Trial Designed?

Group I: Task-specific sham-PCMS, Task-specific PCMS, PCMS-rest Experimental Treatment 3 Interventions

During Task-specific PCMS participants will receive PCMS (TMS + PNS) with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Group II: Task-specific sham-PCMS, PCMS-rest, Task-specific PCMS Experimental Treatment 3 Interventions

During Task-specific PCMS participants will receive PCMS (TMS + PNS) with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Group III: Task-specific PCMS, Task-specific sham-PCMS, PCMS-rest Experimental Treatment 3 Interventions

During Task-specific PCMS participants will receive PCMS (TMS + PNS) with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Group IV: Task-specific PCMS, PCMS-rest, Task-specific sham-PCMS Experimental Treatment 3 Interventions

During Task-specific paired corticospinal-motor neuronal stimulation (PCMS) participants will receive PCMS \[Transcranial Magnetic Stimulation (TMS) + Peripheral Nerve Stimulation (PNS)\] with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Group V: PCMS-rest, Task-specific sham-PCMS, Task-specific PCMS Experimental Treatment 3 Interventions

During Task-specific PCMS participants will receive PCMS (TMS + PNS) with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Group VI: PCMS-rest, Task-specific PCMS, Task-specific sham-PCMS Experimental Treatment 3 Interventions

During Task-specific PCMS participants will receive PCMS (TMS + PNS) with task-specific practice. During PCMS rest participants will receive PCMS (TMS + PNS) without task-specific practice. During Task-specific sham-PCMS participants will receive task-specific practice with sham PCMS (TMS + PNS).

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Amit Sethi

Lead Sponsor

Trials

3

Recruited

60+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

In a study of 17 stroke patients within 10 days of a left hemispheric stroke, transcranial magnetic stimulation (TMS) revealed that the affected hemisphere showed increased excitability, which may impact recovery processes.

The findings suggest that understanding the altered excitatory and inhibitory brain networks during the acute phase after a stroke can help tailor rehabilitation strategies to enhance recovery in the critical first 8-12 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Intracerebral Connectivity in Acute Stroke: A TMS-EEG Study. Tecchio, F., Giambattistelli, F., Porcaro, C., et al.[2023]

In a study involving 10 chronic stroke survivors, it was found that simultaneous contractions of the non-paretic limb during paired associative stimulation (PAS) did not enhance the excitability of corticospinal projections to the impaired limb, suggesting a limitation in targeting specific muscle pathways for rehabilitation.

The results indicate that while PAS alone increased excitability in healthy controls, the combination with non-paretic limb contractions did not yield the same effect in stroke survivors, highlighting the need for more precise methods in non-invasive brain stimulation for effective movement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shaping the Effects of Associative Brain Stimulation by Contractions of the Opposite Limb. Carson, RG., Rankin, ML.[2020]

Transcranial magnetic stimulation (TMS) was used to assess the cortical representation of lower-limb muscles in 16 healthy young adults, but it could not reliably identify distinct cortical areas for these muscles.

The study found variability in the topography of muscle representation across individuals, suggesting that while TMS can provide insights into muscle mapping, it may not be effective for precise identification of muscle-specific cortical areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles. Davies, JL.[2022]

In a pilot study involving six hemiparetic patients with subcortical strokes, paired associative stimulation (PAS) significantly increased motor evoked potentials in the wrist muscles by an average of 78.5% at 5 months post-stroke, indicating enhanced cortical excitability.

The effects of PAS were still observable at 12 months post-stroke, albeit reduced to an average of 30%, suggesting that early intervention with PAS could be beneficial for optimizing motor recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients. Castel-Lacanal, E., Marque, P., Tardy, J., et al.[2022]

Cortical electrical stimulation shows promise as a treatment for upper limb motor impairment after stroke, with evidence suggesting it can enhance motor learning and promote cortical remodeling.

The review covers both transcranial and targeted epidural cortical stimulation techniques, highlighting their potential to modify intracortical circuits and improve recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical brain stimulation: a potential therapeutic agent for upper limb motor recovery following stroke. Harvey, RL., Nudo, RJ.[2016]

The Everest Clinical Trial is a pivotal study involving 174 participants with hemiplegia due to ischemic stroke, testing the safety and efficacy of epidural cortical stimulation combined with rehabilitation for improving upper limb motor function.

Participants in the investigational group will receive cortical stimulation during rehabilitation, with primary outcomes measured at multiple time points to assess significant improvements in motor function, aiming for a clinically meaningful success rate of 20% over the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design for the everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke. Harvey, RL., Winstein, CJ.[2019]

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are promising noninvasive techniques that can modulate brain activity and potentially improve motor function recovery in stroke patients.

These techniques can enhance the effectiveness of rehabilitation training for motor tasks, suggesting they may be integrated into clinical practices to support traditional neurorehabilitation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation in stroke rehabilitation. Webster, BR., Celnik, PA., Cohen, LG.[2022]

Interfering with the activity of the anterior intraparietal sulcus (aIPS) using transcranial magnetic stimulation (TMS) improved tapping performance in stroke patients within the first 10 days after the event, indicating that aIPS may have a maladaptive role early post-stroke.

The study found a significant connection between the connectivity patterns of aIPS, dorsal premotor cortex (dPMC), and the affected primary motor cortex (M1), suggesting that the contralesional aIPS negatively impacts motor performance in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Connectivity-Related Roles of Contralesional Brain Regions for Motor Performance Early after Stroke. Hensel, L., Tscherpel, C., Freytag, J., et al.[2022]

In a rodent model of stroke, combining cortical stimulation with motor rehabilitation significantly improved motor recovery, as evidenced by enhanced performance in a reaching task.

The study showed that cortical stimulation increased the area of the motor cortex that could evoke movement, indicating a physiological benefit that supports recovery of motor function after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult. Kleim, JA., Bruneau, R., VandenBerg, P., et al.[2006]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05736653

NCT05736653 | PCMS Task After Moderate-to-severe Stroke Researchers at the University of Pittsburgh are conducting a research study to see how combining brain, nerve, and hand stimulation affect hand movement ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9509033/

Impact of intensive rehabilitation on long-term prognosis after ... Patients with stroke who received both PT and OT had a better long-term prognosis than those who received either treatment alone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9566624/

Effectiveness of Rehabilitation Exercise in Improving Physical ... Rehabilitation is a crucial part of recovery for stroke survivors, and numerous studies have examined various exercises and treatments of stroke ...

4. mdpi.com mdpi.com/2077-0383/11/8/2149

Benefits from Repetitive Transcranial Magnetic Stimulation ... Post-stroke cognitive dysfunctions occurred in approximately 75% of patients, and half of them can achieve various degrees of cognitive recovery, while the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923000120

Outcomes in Patients with Minor Stroke: Diagnosis and ... Though memory problems are also commonly reported, data regarding outcomes following cognitive rehabilitation programs after stroke in general is also lacking.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3589816/

Longitudinal Changes of Resting-State Functional ... In this study, we explored neural correlates of motor recovery in stroke patients by investigating longitudinal changes in resting-state functional connectivity ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10608684/

Stroke Recovery Is a Journey: Prediction and Potentials of ... According to this rule, the majority of stroke survivors are expected to recover approximately 70% of their maximum potentials at 3 months after ...

8. pnas.org pnas.org/doi/10.1073/pnas.2026676118

Critical Period After Stroke Study (CPASS): A phase II ... Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained ...