Neurostimulation for Respiratory Function After Spinal Cord Injury

Sponsor

Shirley Ryan AbilityLab (Other)

Overall Status

Recruiting

CT.gov ID

NCT05756894

Collaborator

(none)

Enrollment

Location

Arm

46.1

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries Cervical Spinal Cord Injury Respiratory Function Impaired	Device: Neurostimulation Other: Repiratory training	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Participants with high cervical spinal cord injury will receive 40 treatment sessions (STDP stimulation and respiratory training) and will be asked to complete pre-, Post-20, and Post-40 assessment sessions.Participants with high cervical spinal cord injury will receive 40 treatment sessions (STDP stimulation and respiratory training) and will be asked to complete pre-, Post-20, and Post-40 assessment sessions.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 28, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change in Motor evoked potentials (MEPs) [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.]
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.
Change in Maximum Voluntary Contractions (MVCs) [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.]
Individuals will perform a maximum voluntary contraction (MVC) of diaphragm muscle through surface electrodes secured to the skin over the chest and belly region.

Secondary Outcome Measures

Change in Cervicomedullary electric potentials (CMEPs) [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.]
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.
Change in Pulmonary function tests [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.]
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 the Diaphragm ultrasound imaging [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.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and females between ages 18-85 years
SCI at least 6 months post-injury
Spinal Cord injury at C1-C5
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)
Must have a family member or caregiver who is trained and willing to operate the mechanical ventilator during study visits.

Exclusion Criteria:

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.
Any debilitating disease prior to the SCI that caused exercise intolerance.
Individuals entirely dependent on the support of a diaphragmatic pacer (24 hours per day).
Premorbid, ongoing major depression or psychosis, altered cognitive status.
History of head injury or stroke
Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without a history of seizure, and without anticonvulsant medication
History of seizures or epilepsy
Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold
Pregnant females
If a woman of childbearing age is unsure of the pregnancy, and does not want to take the pregnancy test
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
Metal plate in skull
Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
Individuals taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs