Neurostimulation for Respiratory Function After Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05756894
• Other study ID #: STU00217043
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2023
• Source: Shirley Ryan AbilityLab
• Contact: Monica A Perez, PT, PhD
• Phone: 3122382886
• Email: mperez04[@]sralab.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Spinal Cord Injury
• Respiratory Function Impaired
• Respiratory Insufficiency
• Spinal Cord Injuries
• Wounds and Injuries

Intervention

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:
• 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.

Locations

Country	Name	City	State
United States	Shirley Ryan Ability Lab	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Shirley Ryan AbilityLab

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.