Brain State-dependent PCMS in Chronic Stroke

Upregulating Corticospinal Function After Stroke Using Brain State-dependent Paired Corticomotoneuronal Stimulation

After stroke, people often have difficulty using their hands. Combined brain and nerve stimulation can strengthen the neural pathways that control hand function. In this study, we will deliver combined brain and nerve stimulation during specific time windows that increase activation of neural pathways underlying hand function. We will compare the effects of combined brain and nerve stimulation during these optimal time windows to the effects of combined brain and nerve stimulation applied during random time windows on post-stroke hand function.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke
• Intervention / Treatment: Combination product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS)

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas at Austin
      • Contact: Sara Hussain; Phone Number: 512-232-2686; Email: sara.hussain@austin.utexas.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of stroke > 6 months ago
• Presence of residual upper extremity hemiparesis
• Willingness to participate
• Ability to provide informed consent
• Upper extremity Fugl-Meyer score < 66
• Mini Mental State Exam score > 24
• Discernible and reliable motor-evoked potential (MEP) elicited following single-pulse TMS to the lesioned hemisphere

Exclusion Criteria:

• History of neurological disease other than stroke
• Presence of contraindications to transcranial magnetic stimulation (TMS) or peripheral nerve stimulation (PNS), including: history of adverse reactions to TMS or PNS metal in head, eyes, neck, chest/trunk, or arms, including but not limited to shrapnel, surgical clips, fragments from metalworking, fragments from welding, implanted device, history of frequent and severe headaches or migraines, immediate family history of seizure or epilepsy, personal history of seizure or epilepsy, current, suspected, or planned pregnancy, current or recent (within the last 3 months) use of medications acting on the central nervous system other than selective serotonin reuptake inhibitors (SSRIs), including but not limited to antipsychotic drugs, benzodiazepines, prescription stimulants.
• Upper extremity Fugl-Meyer score ≥ 66 (66 is the maximum on this scale)
• Mini Mental State Exam score <= 24
• No discernible and reliable MEP elicited following single-pulse TMS to the lesioned hemisphere

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCMS during brain states reflecting strong corticospinal transmission	Combination product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS); Paired corticomotoneuronal stimulation (PCMS) involves delivering precisely timed pairs of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) so that the neuronal activity evoked by such stimulation arrives synchronously at corticospinal-motoneuronal synapses. This synchronous arrival is postulated to cause long-term potentiation via spike timing-dependent plasticity, which then improves corticospinal transmission and hand function. In this study, paired corticomotoneuronal stimulation (PCMS) will be applied during specific brain states that reflect increased recruitment of motoneurons via the corticospinal tract. This increased recruitment is expected to enhance the beneficial effects of PCMS on human hand function after stroke.
Active Comparator: PCMS during random brain states	Combination product: Brain state-dependent paired corticomotoneuronal stimulation (PCMS); Paired corticomotoneuronal stimulation (PCMS) involves delivering precisely timed pairs of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) so that the neuronal activity evoked by such stimulation arrives synchronously at corticospinal-motoneuronal synapses. This synchronous arrival is postulated to cause long-term potentiation via spike timing-dependent plasticity, which then improves corticospinal transmission and hand function. In this study, paired corticomotoneuronal stimulation (PCMS) will be applied during specific brain states that reflect increased recruitment of motoneurons via the corticospinal tract. This increased recruitment is expected to enhance the beneficial effects of PCMS on human hand function after stroke.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum hand force output	This will be measured using maximum voluntary contractions of the stroke-affected first dorsal interosseous hand muscle during pinching actions.	up to 1 hour after intervention
Maximum hand muscle activation	This will be measured using electromyography recordings of the stroke-affected first dorsal interosseous muscle during maximum voluntary contractions during pinching actions	up to 1 hour after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amplitude of motor evoked potentials	This will be measured as the peak-to-peak amplitude of motor-evoked potentials recorded from the stroke-affected first dorsal interosseous muscle	up to 1 hour after intervention
Time to complete the 9-hole peg test	This will be measured as the time needed to complete the task using the stroke-affected hand.	up to 1 hour after intervention

Collaborators and Investigators

• Sponsor: University of Texas at Austin

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: chronic, movement
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: STUDY00000896_Exp3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be shared using an open-access data repository. No personally-identifiable information will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No