Non-Invasive Interventions for Respiratory Recovery in Chronic Spinal Cord Injury

NCT07135583 | Recruiting DMC

• 2 other identifiers: IRBID-2023-17961349389
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal cord injuries (SCI) can seriously affect a person's ability to breathe. This happens because the injury can damage the nerves that control the muscles used for breathing. As a result, people with SCI often face breathing problems, a higher risk of lung infections, and even early death. While breathing exercises can help strengthen these muscles, they often aren't intense enough to make a big difference, especially in people with long-term injuries. This research project is exploring a new way to improve breathing in people with chronic SCI. The goal is to "wake up" the remaining nerve pathways that still connect the brain and spinal cord to the breathing muscles. By doing this, the investigators hope to make breathing exercises more effective and improve overall respiratory health. The investigators are testing a combination of two non-invasive (non-surgical) techniques: Transcutaneous Spinal Cord Stimulation (tSCS): This uses small electrical pulses delivered through the skin to stimulate the spinal cord and help activate the muscles used for breathing. Hypercapnic-Hypoxia Protocol (HiCO₂-AIH): This involves breathing air with lower oxygen and higher carbon dioxide for short periods. This naturally increases the brain's drive to breathe and may help strengthen the breathing muscles. The investigators believe that using these two techniques together will "prime" the nervous system, making it more responsive to breathing exercises. This could lead to better outcomes for people with SCI. In addition to testing this treatment, the investigators are also collecting saliva and blood samples to look for biomarkers-biological clues that might help predict who will benefit most from this therapy. These include genetic markers and signs of nerve damage in the blood. Who Can Participate The investigators are looking for adults aged 18 to 70 who: Have had a spinal cord injury for at least one year. Have an injury between the neck and upper back (from C3 to T8). Have an incomplete injury (some nerve function remains). Are medically stable and cleared by a doctor. Have at least a 20% reduction in breathing strength. What Participants Will Do Each participant will complete four rounds of treatment. Each round includes four days in a row of therapy, followed by a three-week break before the next round. Each daily session lasts about two hours and includes: Breathing special air mixtures (low oxygen and high carbon dioxide) for short periods, followed by normal air. A short break. Then, spinal cord stimulation combined with breathing exercises that use resistance (like breathing through a straw). What the Investigators Will Measure The investigators will track: Breathing ability using lung function tests and pressure measurements. Nerve activity using brain and spinal cord stimulation to see how well the diaphragm (the main breathing muscle) responds. Safety by monitoring oxygen levels, heart rate, blood pressure, and breathing responses during each session. Biological Samples Participants will provide: A one-time saliva sample for genetic testing. A one-time blood sample to look for markers of nerve injury. Why This Matters This study could lead to new, non-invasive treatments that improve breathing and quality of life for people living with spinal cord injuries. By identifying who is most likely to benefit from this therapy, the investigators can also move toward more personalized and effective care in the future.

Conditions

Spinal Cord Injury, Chronic; Spinal Cord Injury Cervical; Spinal Cord Injury Thoracic; Incomplete Spinal Cord Injury

Keywords

"Spinal Cord Stimulation" [MeSH]; acute intermittant hypoxia; respiratory resistance training; Genetic Biomarker; Blood biomarker

Outcome Measures

Primary Outcomes (1)

• change in mouth occlusion pressure at 0.1 secs (P0.1)

  It measures the pressure generated at the mouth in the first 0.1 second of inspiration when the airway is unexpectedly occluded at the end of expiration. The negative pressure generation in 0.1 seconds reflects respiratory motor drive without time for modification by sensory systems such as lung stretch or visual input. The inspiratory valve will be occluded prior to the onset of inspiration, without participant awareness, and maintained until the subsequent inspiratory effort. Negative pressure generation will be recorded using a pressure transducer connected to a non-rebreathable mask. All respiratory assessments will be performed in accordance with standard testing guidelines. Measurement indices of ventilation will be obtained using a mouthpiece attached to the pneumotach and nasal clips. The mouth pressure from the pneumotach will be converted to a digital signal using Powerlab C.

  Pre- Baseline (Day 1), Post 1(30 minute post day 4 intervention) and Post 2 ( 24 hours post day 4 intervention)

Secondary Outcomes (4)

• Maximum Inspiratory (MIP) & Expiratory (MEP) Pressure

  Pre- Baseline (Day 1), Post 1(30 minute post day 4 intervention) and Post 2 ( 24 hours post day 4 intervention)

• Sniff nasal inspiratory pressure (SNIP)

  Pre- Baseline (Day 1), Post 1(30 minute post day 4 intervention) and Post 2 ( 24 hours post day 4 intervention)

• Transcranial Magnetic Stimulation (TMS) evoked Diaphragm Motor Evoked Potentials

  Pre- Baseline (Day 1), Post 1(30 minute post day 4 intervention) and Post 2 ( 24 hours post day 4 intervention)

• Cervical Magnetic Stimulation (CMS) Diaphragm motor evoked potentials

  Pre- Baseline (Day 1), Post 1(30 minute post day 4 intervention) and Post 2 ( 24 hours post day 4 intervention)

Study Arms (4)

Combined Intervention

EXPERIMENTAL

Experimental Combination of HiCO2-AIH+ tSCS paired respiratory exercise

Other: Active Comparator: Single Intervention 1; Other: Active Comparator: Single Intervention 2; Behavioral: Respiratory Resistance Exercise

Single Intervention 1

ACTIVE COMPARATOR

Combination of HiCO2-AIH+ Sham stimulation paired respiratory exercise

Other: Active Comparator: Single Intervention 1; Behavioral: Respiratory Resistance Exercise

Single Intervention 2

ACTIVE COMPARATOR

Combination of Sham Exposure + tSCS paired respiratory exercise

Other: Active Comparator: Single Intervention 2; Behavioral: Respiratory Resistance Exercise

Sham Intervention

PLACEBO COMPARATOR

Combination of Sham Exposure + Sham Stimulation paired respiratory exercise

Behavioral: Respiratory Resistance Exercise

Interventions

Active Comparator: Single Intervention 1 OTHER

Acute intermittent hypercapnic-hypoxia (15 episodes of 1.5 minute O2= 9%, CO2=4% and balance N2, interspaced with 1.5 min room air

Combined Intervention; Single Intervention 1

Active Comparator: Single Intervention 2 OTHER

An open-loop continuous tSCS stimulation \[30 min duration, low frequency (30 Hz), tolerable intensity (\~10-15 mA), 400 µsec pulse width, biphasic symmetric waveform\] will be delivered using 2 channels: Channel 1- C4-C5 spine; Channel 2- T4 spine; returning electrodes at ASIS.

Combined Intervention; Single Intervention 2

Respiratory Resistance Exercise BEHAVIORAL

Respiratory strength training will be conducted using a standard, spring-loaded threshold device while the participant is receiving either tSCS or Sham tSCS. Participants will complete one warm-up set at a pressure threshold approximately 40% of their pre-test outcomes (obtained on day 1 of the corresponding intervention block) for maximal inspiratory and expiratory pressure generation. Following the warm-up, participants will train at a pressure threshold approximately 70% of their pre-test outcomes and will complete three sets of 6-12 repetitions for both inspiratory and expiratory strength training. A training breath will consist of a \~1-2-second sustained effort through the device, separated by 5-10 seconds of quiet breathing. The order of the three sets each of inspiratory or expiratory training will alternate for each of the five daily sessions; the order on day 1 of training will be randomly determined.

Also known as: Respiratory Strength Training, Inspiratory resistance training, Expiratory resistance training

Combined Intervention; Sham Intervention; Single Intervention 1; Single Intervention 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults 18 to 70 years of age (the latter to reduce likelihood of cardiovascular disease);
• chronic SCI for ≥ 1 year at or below C-3 to T-8
• incomplete SCI based on classification of incomplete-B, C or D
• medically stable with clearance from physician
• SCI due to non-progressive etiology
• \>20% impairment in maximal inspiratory or expiratory pressure generation

You may not qualify if:

• Individuals will be excluded due to (1) current diagnosis of an additional neurologic condition (eg. multiple sclerosis or stroke) (2) loss of diaphragm EMG activity on forced respiratory tests; (3) severe illness or infection (4) non-healing decubitus ulcers (5) untreated bladder or urinary infections (6) cardiovascular disease (7) lung disease (8) active heterotopic ossification (9) uncontrolled hypertension; (10) severe neuropathic pain; (11) pregnancy (5) severe recurrent and uncontrolled autonomic dysreflexia (6) history of seizure disorder.

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University Center City Campus

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries; Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Jay Nair, PT, PhD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jay Nair, PT, PhD

CONTACT

13528715888; nairlab@jefferson.edu

Dana R Johnson, PT, DPT

CONTACT

215-326-9153; jayakrishnan.nair@jefferson.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: A Single-blind, placebo-controlled, randomized order, William Latin cross-over experimental design

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 22, 2025
• Study Start: September 18, 2025
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): August 15, 2027
• Last Updated: February 5, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be made available within 1 year of the completion of the study (Aug 2028).
• Access Criteria: Data on Open Data Commons for Spinal Cord Injury (ODC-SCI) or similar site will be open to public and any researcher

Locations

US (1)