Neurostimulation for Respiratory Function After Spinal Cord Injury

Pilot Study: Spike-timing-dependent Plasticity for Respiratory Function After Spinal Cord Injury

The purpose of this research study is to learn more about the connections between the brain, nerves, and diaphragm after experiencing a cervical spinal cord injury (SCI).The main question it aims to answer is:

Changes in respiratory function and recovery using stimulation and respiratory exercise training in spinal cord-injured individuals.

Participants will complete a maximum of 55 study visits. They will be asked to complete about 40 treatment sessions which include multiple stimulation sessions over the scalp and neck, followed by about 60 minutes of respiratory training. Assessment sessions will be completed prior at baseline, after 20 sessions and after 40 sessions of study treatment.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries; Cervical Spinal Cord Injury; Respiratory Function Impaired
• Intervention / Treatment: Device: Neurostimulation; Other: Repiratory training

Detailed Description

The purpose of this study is to test a strategy to potentiate functional recovery of respiratory function in individuals with spinal cord injury (SCI). Respiratory function is often impaired in individuals with high cervical spinal cord injury (SCI, C1-C5) leading to reduced quality of life and mortality. Currently, research has shown Spike-timing-dependent plasticity (STDP) targeting cortico-motoneuronal connections effectively promote recovery in upper and lower limbs, including functions such as grasping and locomotion. The overall goal of our proposal is to develop a non-invasive protocol using

STDP that can be used to strengthen synaptic plasticity and voluntary motor output in the diaphragm muscle in humans with high cervical SCI. To assess the effect of STDP on respiratory function in humans with high cervical SCI, we propose a pilot study of efficacy trial with the specific aim below:

The overall objective of this project is to investigate the efficacy of spike-timing-dependent plasticity (STDP) on respiratory function in humans with high cervical SCI.

Specific Aim: Examine the effect of STDP in respiratory function in humans with chronic high cervical SCI.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Monica A Perez, PT, PhD; Phone Number: 3122382886; Email: mperez04@sralab.org
• Study Contact Backup: Name: Sri Ramya Vemulakonda, M.B.B.S; Phone Number: 3122382993; Email: svemulakon@sralab.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Shirley Ryan Ability Lab
      • Contact: Sri Ramya Vemulakonda, MBBS; Phone Number: 312-238-2993; Email: svemulakon@sralab.org
      • Contact: Monica Perez, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and females between ages 18-85 years
2. SCI at least 6 months post-injury
3. Spinal Cord injury at C1-C5
4. Demonstrate respiratory deficit following spinal cord injury as following: (1) Individuals using mechanical ventilation, and (2) individuals with pulmonary function testing (PFT) deficits corresponding to having a vital capacity (VC) < 80% (predicted)
5. Must have a family member or caregiver who is trained and willing to operate the mechanical ventilator during study visits.

Exclusion Criteria:

1. Any illness or condition that based on the research team's assessment, will compromise with the participant's ability to comply with the protocol, patient safety, or the validity of the data collected during this study.
2. Any debilitating disease prior to the SCI that caused exercise intolerance.
3. Individuals entirely dependent on the support of a diaphragmatic pacer (24 hours per day).
4. Premorbid, ongoing major depression or psychosis, altered cognitive status.
5. History of head injury or stroke
6. Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without a history of seizure, and without anticonvulsant medication
7. History of seizures or epilepsy
8. Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold
9. Pregnant females
10. If a woman of childbearing age is unsure of the pregnancy, and does not want to take the pregnancy test
11. Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
12. Metal plate in skull
13. Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
14. Individuals taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neurostimulation for respiratory function after spinal cord injury; Efficacy of STDP on respiratory function.

Device: Neurostimulation; Paired stimulation will be given to the spinal cord and to peripheral nerves so that the signals are received at the spinal cord at a specific interval.; Other Names: Spike-timing-dependent plasticity (STDP stimulation); Neural plasticity; Other: Repiratory training; Respiratory exercises will be completed immediately after completing neurostimulation. Respiratory exercises will involve inspiratory muscle training performing four sets of 6-10 breaths per day with two minutes of rest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Motor evoked potentials (MEPs)	Transcranial magnetic stimuli (TMS) will be delivered to the optimal scalp position for activation of the diaphragm muscle. The optimal scalp position will be determined by moving the coil in small steps along the diaphragm representation of the primary motor cortex to find the region where the largest MEP can be evoked with the minimum intensity in the targeted muscles.	MEPs measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.
Change in Maximum Voluntary Contractions (MVCs)	Individuals will perform a maximum voluntary contraction (MVC) of diaphragm muscle through surface electrodes secured to the skin over the chest and belly region.	MVCs measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cervicomedullary electric potentials (CMEPs)	Transcranial magnetic stimuli will be delivered to the optimal position of the cervical spine. A small device on the surface of the skin behind the ear will deliver pulses of electricity over the back of the neck.	CMEPs measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.
Change in Pulmonary function tests	Spirometry will be tested in upright and supine position to measure negative inspiratory force (NIF), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and their ration (FEV1/FVC)	Change in pulmonary function tests measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.
Change in the Diaphragm ultrasound imaging	Ultrasound imaging will be acquired for optimal visualization of each hemidiaphragm. The diaphragm will be examined during quiet breathing and during maximal inspiration. MVCs measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.	Change in the diaphragm ultrasound imaging measured at baseline, 7 weeks (20 sessions), and 14 weeks (40 sessions) of STDP stimulation and respiratory training for the participants during study procedures.

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab
• Investigators: Principal Investigator: Monica A Perez, PT, PhD, Shirley Ryan AbilityLab

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Spinal cord injury; Diaphragm; Respiratory training; Neurostimulation; Neural plasticity; Spike-timing-dependent plasticity
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Trauma, Nervous System; Spinal Cord Diseases; Respiratory Insufficiency; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: STU00217043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No