Peripheral Nerve Stimulation and Motor Training in Stroke

Peripheral Nerve Stimulation and Motor Training to Enhance Hand Function After Stroke

Cerebrovascular disease is a major cause of disability worldwide. The catastrophic burden of stroke is more dramatic in low- and middle- income countries, and the scarcity of evidence-based rehabilitation interventions represents a major challenge to global health care. Upper limb weakness is frequent after stroke, but there is no universally accepted treatment to effectively improve hand function in patients with moderate and severe motor impairment. These are the patients in deepest need of rehabilitative interventions. This project addresses this important issue, by testing effects of a novel approach. The investigators will non-invasively stimulate peripheral nerves in order to enhance effects of motor training aided by an electrical stimulation device in patients with moderate to severe hand weakness. Our hypothesis is that peripheral nerve stimulation will enhance effects of motor training in patients in the chronic stage after stroke.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: PNS

Detailed Description

The objective of this protocol is to determine whether a neuromodulation intervention associated with functional electrical stimulation, when combined with task-specific training over several sessions, decreases upper limb motor disability, motor impairment, overall disability and improves quality of life compared to the sham intervention and functional electrical stimulation.

The interventions will consist of three sessions per week, over six weeks, of outpatient functional electrical stimulation of the paretic wrist and task-specific training. In each session, either active peripheral nerve stimulation (PNS) or sham PNS will be applied. Before the first session, patients will be familiarized with the procedures.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05403000
      • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo/Fundação Faculdade de Medicina

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:

• Age, 18 years or older;
• Ischemic or hemorrhagic stroke at least six months before, confirmed by computed tomography or magnetic resonance imaging;
• Moderate to severe motor impairment of an upper limb, defined as a score between 7 and 50 on the Fugl-Meyer Assessment of Sensorimotor Recovery after stroke, a scale with scores for upper limb ranging from 0 (no function) to 66 (normal function);
• Ability to provide written Informed Consent (patient or legal representative);
• Ability to comply with the schedule of interventions and evaluations in the protocol.

Exclusion Criteria:

• Lack of ability to voluntarily activate any active range of wrist extension;
• Anesthesia of the paretic hand;
• Severe spasticity at the paretic elbow, wrist, or fingers, defined as a score of >3 on the Modified Ashworth Spasticity Scale;
• Active joint deformity;
• Uncontrolled medical problems such as end-stage cancer or renal disease;
• Pregnancy;
• Seizures, if current use of drugs that may decrease seizure threshold such as tryciclic antidepressants;
• Pacemakers;
• Other neurological disorders such as Parkinson's disease;
• Psychiatric illness including severe depression;
• Aphasia or serious cognitive deficits that preclude comprehension of the experimental protocol or ability to provide consent;
• Treatment of upper limb spasticity with botulinum toxin within the past three months.
• Lesions that affect the cerebellum or cerebelar/vestibular pathways in the brainstem

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active PNS; Active PNS will be administered by 2 pairs of surface electrodes (cathode proximal). One pair will overly the median and ulnar nerves at the wrist, and the other pair will overly the radial nerve. Trains of electric stimulation will be delivered at 1 Hz by using isolation units connected to a square pulse stimulator.	Procedure: PNS; Active PNS will be administered by 2 pairs of surface electrodes (cathode proximal). One pair will overly the median and ulnar nerves at the wrist, and the other pair will overly the radial nerve. Trains of electric stimulation will be delivered at 1 Hz by using isolation units connected to a square pulse stimulator. In sham PNS, the median, ulnar and radial nerves will not be actively stimulated.; Other Names: Peripheral Nerve Stimulation
Placebo Comparator: Sham PNS; In sham PNS, the median, ulnar and radial nerves will not be actively stimulated.	Procedure: PNS; Active PNS will be administered by 2 pairs of surface electrodes (cathode proximal). One pair will overly the median and ulnar nerves at the wrist, and the other pair will overly the radial nerve. Trains of electric stimulation will be delivered at 1 Hz by using isolation units connected to a square pulse stimulator. In sham PNS, the median, ulnar and radial nerves will not be actively stimulated.; Other Names: Peripheral Nerve Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wolf Motor Function Test	The primary outcome will be evaluated before the intervention and 6 weeks after the beginning of the intervention.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Activity Log	This questionnaire will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Active range of motion of wrist extension in the paretic side	This physiological parameter will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Active range of motion of wrist flexion in the paretic side	This physiological parameter will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Grasp force in the paretic side	This physiological parameter will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Grip force in the paretic side	This physiological parameter will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Fugl-Meyer Assessment of Sensorimotor Recovery	This scale will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Barthel Index	This scale will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Stroke Impact Scale	This scale will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Beck Depression Inventory-short Form	This questionnaire will be evaluated before the intervention and 3, 6, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Wolf Motor Function Test	This scale as a secondary outcome will be evaluated before the intervention and 3, 10 and 18 weeks after the beginning of the intervention.	18 weeks
Modified Ashworth Scale	This scale will be evaluated before the intervention and 3, 6, 10 and 18 weeks	18 weeks
Minimal Clinically Important Difference - Wolf Motor Function Test - time	This outcome will be evaluated at 6, 10 and 18 weeks	18 weeks
Minimal Clinically Important Difference - Wolf Motor Function Test - Functional Ability Scale	This outcome will be evaluated at 6, 10 and 18 weeks	18 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); The Cleveland Clinic; Fundação Faculdade de Medicina
• Investigators: Principal Investigator: Adriana Conforto, MD PhD, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo/ Fundação Faculdade de Medicina

Publications and helpful links

General Publications

• Conforto AB, Machado AG, Ribeiro NHV, Plow EB, Liew SL, da Costa Leite C, Zavaliangos-Petropulu A, Menezes I, Dos Anjos SM, Luccas R, Peckham PH, Cohen LG. Repetitive Peripheral Sensory Stimulation as an Add-On Intervention for Upper Limb Rehabilitation in Stroke: A Randomized Trial. Neurorehabil Neural Repair. 2021 Dec;35(12):1059-1064. doi: 10.1177/15459683211046259. Epub 2021 Sep 29.
• Conforto AB, Machado AG, Menezes I, Ribeiro NHV, Luccas R, Pires DS, Leite CDC, Plow EB, Cohen LG. Treatment of Upper Limb Paresis With Repetitive Peripheral Nerve Sensory Stimulation and Motor Training: Study Protocol for a Randomized Controlled Trial. Front Neurol. 2020 Mar 25;11:196. doi: 10.3389/fneur.2020.00196. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: January 14, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 0546/2011; R01NS076348 (U.S. NIH Grant/Contract)