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

Trial Summary

What is the purpose of this trial?

Researchers at the University of Pittsburgh are conducting a research study to see how combining brain, nerve, and hand stimulation affect hand movement after stroke. The primary purpose of this study is to examine changes in the connection between the brain and the weak hand muscles after the combined brain, nerve, and hand stimulation. The primary hypothesis is that the combined brain, nerve, and hand stimulation will increase the the connection between the brain and the weak hand muscles. The secondary purpose of this study is to examine changes in weak hand's movement and function after the combined brain, nerve, and hand stimulation. The secondary hypothesis is that the combined brain, nerve, and hand stimulation will increase weak hand movement and function.

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 data supports the effectiveness of the treatment Paired Associative Stimulation for Post-Stroke Recovery?

Research shows that combining cortical stimulation with rehabilitation can improve arm function after a stroke. Noninvasive brain stimulation techniques like transcranial magnetic stimulation (TMS) can enhance motor recovery by increasing brain activity related to movement, which is beneficial for stroke rehabilitation. ^{1 2 3 4 5}

Is Paired Associative Stimulation safe for humans?

Research on noninvasive brain stimulation techniques, like Paired Associative Stimulation, suggests they are generally safe for humans, as they modulate brain activity without surgery. These methods have been used in both healthy individuals and stroke patients to enhance motor function recovery. ^{1 2 4 6 7}

How is the treatment Task-specific PCMS different from other treatments for post-stroke recovery?

Task-specific PCMS is unique because it combines peripheral nerve stimulation with transcranial magnetic stimulation (TMS) to specifically target and enhance the brain's ability to reorganize and improve motor function after a stroke. This approach aims to induce long-term changes in brain activity, which is different from other treatments that may not focus on such targeted neural plasticity. ^{1 4 7 8 9}

Research Team

Amit Sethi, PhD

Principal Investigator

University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Design for the everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation in stroke rehabilitation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult. [2006]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Shaping the Effects of Associative Brain Stimulation by Contractions of the Opposite Limb. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effective Intracerebral Connectivity in Acute Stroke: A TMS-EEG Study. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Connectivity-Related Roles of Contralesional Brain Regions for Motor Performance Early after Stroke. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Cortical brain stimulation: a potential therapeutic agent for upper limb motor recovery following stroke. [2016]