Repetitive Nerve Stimulation to Improve Recovery After Stroke (RESTORES)

Comparison Between Mechanisms Underlying Effects of Repetitive Peripheral Nerve Stimulation on Upper Limb Motor Performance in the Subacute and Chronic Phases After Stroke

Upper limb paresis is the most common type of post-stroke neurological impairment and a major cause of functional disability. Repetitive peripheral electrical stimulation (RPES) is a novel strategy to improve upper limb motor performance in the post-stroke chronic phase but its effects in the subacute phase are still poorly understood. The objectives of this study are to compare the effects of RPES on motor performance of the upper limb in the subacute and chronic phases of stroke, and to identify the mechanisms underlying this intervention.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: Repetitive peripheral nerve stimulation; Device: Sham Repetitive peripheral nerve stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adriana Conforto; Phone Number: +55-11-21519542; Email: adrianabc@einstein.br
• Study Contact Backup: Name: Larissa Servinsckins; Phone Number: +55-11-21513354; Email: larissa.servinsckins@einstein.br

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Recruiting
      • Hospital Sao Rafael
      • Contact: Suzete N da Guarda, Prof; Phone Number: +55-71-3409-8000; Email: suzetefariasdaguarda@icloud.com
  • SP
    • São Paulo, SP, Brazil, 05.652-000
      • Recruiting
      • Hospital israelita Albert Einstein
      • Contact: Adriana B Conforto, Prof; Phone Number: +55-11-21519542; Email: adriana.conforto@einstein.br
      • Contact: Jesica B Kroth, PT; Phone Number: +55-11-21519542; Email: jessicakroth@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ischemic or hemorrhagic stroke confirmed by computed tomography or magnetic resonance imaging, between 7 days - 3 months before enrollment (subacute phase), and at least 6 months (chronic phase).
• Ability to perform at least 4 of 7 tasks performed in daily life that is part of the Jebsen-Taylor Test

Exclusion Criteria:

• Anesthesia of the paretic hand.
• Lesions affecting the motor cortex (hand area).
• Lesions affecting cerebellum, or cerebellar pathways in the brainstem.
• Severe spasticity at the paretic elbow, fist or fingers, defined with a score larger than 3 on the Modified Ashworth Scale.
• Neurological diseases such as Parkinson disease or chronic uncontrolled chronic disease such as cancer or cardiac insufficiency.
• Elbow pain or join deformity in the paretic limb.
• Pregnancy.
• Uncontrolled psychiatric disease.
• Aphasia or severe cognitive deficit.
• Inability to provide consent.
• Inability to attend the experimental sessions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active, subacute stroke; Repetitive peripheral electrical stimulation (RPES) + Motor Training. Active RPES will be administered for 2 hours. After active session of RPES, the patient will receive motor training.	Device: Repetitive peripheral nerve stimulation; Active repetitive peripheral nerve stimulation will be applied to the median nerve of the affected forearm with surface electrodes. The stimulator will be set to deliver bursts of 10 Hz stimulation at 50% duty cycle (500 ms on and off). For active stimulation, intensities will be set at the highest intensity able to induce sensory paraesthesias without overt muscle contraction or pain, and adjusted if required.
Sham Comparator: Sham, subacute stroke; Sham Comparator: Sham + Motor Training. Sham will be administered for 2 hours. After sham, the patient will receive motor training	Device: Sham Repetitive peripheral nerve stimulation; Sham repetitive peripheral nerve stimulation will be applied to the median nerve of the affected forearm with surface electrodes. The stimulator will be set to deliver bursts of 10 Hz stimulation at 50% duty cycle (500 ms on and off). For sham stimulation, intensities will be set at 10mv - 15mv lower than de lowest intensity able to induce sensory paraesthesias, and adjusted if required.
Active Comparator: Active, chronic stroke; Repetitive peripheral electrical stimulation (RPES) + Motor Training. Active RPES will be administered for 2 hours. After active session of RPES, the patient will receive motor training.	Device: Repetitive peripheral nerve stimulation; Active repetitive peripheral nerve stimulation will be applied to the median nerve of the affected forearm with surface electrodes. The stimulator will be set to deliver bursts of 10 Hz stimulation at 50% duty cycle (500 ms on and off). For active stimulation, intensities will be set at the highest intensity able to induce sensory paraesthesias without overt muscle contraction or pain, and adjusted if required.
Sham Comparator: Sham, chronic stroke; Sham Comparator: Sham + Motor Training. Sham will be administered for 2 hours. After sham, the patient will receive motor training	Device: Sham Repetitive peripheral nerve stimulation; Sham repetitive peripheral nerve stimulation will be applied to the median nerve of the affected forearm with surface electrodes. The stimulator will be set to deliver bursts of 10 Hz stimulation at 50% duty cycle (500 ms on and off). For sham stimulation, intensities will be set at 10mv - 15mv lower than de lowest intensity able to induce sensory paraesthesias, and adjusted if required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Jebsen-Taylor Test	Test of upper limb dexterity	Immediately after one session of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lateral pinch strength	Pinch strength measured with dynamometer	Immediately after one session of intervention
Change in gamma-aminobutyric acid levels in primary motor cortex	Gamma-aminobutyric acid levels measured with magnetic resonance imaging spectroscopy	Immediately after one session of intervention
Change in brain perfusion	Brain perfusion measured with magnetic resonance imaging - arterial spin labeling	Immediately after one session of intervention
Change in grasp strength	Grasp strength measured with dynamometer	Immediately after one session of intervention

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo

Publications and helpful links

General Publications

• Kroth JB, Handfas B, Rodrigues G, Zepeda F, Oliveira MA, Wang DJJ, de Azevedo Neto RM, Silva GS, Amaro E Jr, Sorinola IO, Conforto AB. Effects of Repetitive Peripheral Sensory Stimulation in the Subacute and Chronic Phases After Stroke: Study Protocol for a Pilot Randomized Trial. Front Neurol. 2022 Feb 16;13:779128. doi: 10.3389/fneur.2022.779128. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Rehabilitation; Neuromodulation; Motor function; Peripheral stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 3019629

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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