Non-Invasive Interventions for Respiratory Recovery in Chronic Spinal Cord Injury
NCT ID: NCT07135583
Last Updated: 2026-02-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
20 participants
INTERVENTIONAL
2025-09-18
2027-08-15
Brief Summary
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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.
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Detailed Description
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To determine whether combining hypercapnic-hypoxia protocol (HiCO₂-AIH) and transcutaneous spinal cord stimulation (tSCS) can enhance the effects of respiratory resistance training in individuals with chronic spinal cord injury (SCI).
To explore whether genetic and blood-based biomarkers can help predict how individuals respond to this combined intervention.
We will test these objectives in adults with chronic SCI using a Williams cross-over design. The study will include 16 participants (with statistical power \>0.8 and α=0.05), accounting for a 20% dropout rate, for a total enrollment of 20 participants.
Specific Aims
Aim 1:
To determine whether four consecutive days of combined HiCO₂-AIH and tSCS will improve the effectiveness of respiratory resistance training compared to either intervention alone.
Outcomes (measured from PRE to 1 day POST intervention):
Primary Outcome: Change in mouth occlusion pressure at 0.1 seconds (P0.1). Secondary Outcomes: Maximal inspiratory and expiratory pressure generation, forced vital capacity (FVC), neurophysiological measures of cortico-spinal drive (amplitude of transcranial magnetic stimulation \[TMS\]) and local spinal excitability (amplitude of cervical magnetic stimulation \[CMS\]) in the diaphragm.
Safety Outcomes: Continuous monitoring of respiratory parameters (end tidal oxygen \[O₂\] and carbon dioxide \[CO₂\] concentration, oxygen saturation \[SpO₂\]) and cardiovascular parameters (blood pressure \[BP\], heart rate \[HR\], and electrocardiogram \[ECG\]) during each session.
Aim 2:
To identify predictive factors for treatment response to the combined HiCO₂-AIH and tSCS intervention using:
1. Genetic polymorphisms related to intermittent hypoxia signaling pathways.
2. Molecular markers of neurotrauma and inflammation found in blood extracellular vesicles (EVs).
Outcomes:
Regression analyses will be conducted to examine the relationship between treatment outcomes and:
Specific genetic single nucleotide polymorphisms (SNPs). Blood-based molecular markers of neurotrauma and inflammation.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
SINGLE
Study Groups
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Combined Intervention
Experimental Combination of HiCO2-AIH+ tSCS paired respiratory exercise
Active Comparator: Single Intervention 1
Acute intermittent hypercapnic-hypoxia (15 episodes of 1.5 minute O2= 9%, CO2=4% and balance N2, interspaced with 1.5 min room air
Active Comparator: Single Intervention 2
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.
Respiratory Resistance Exercise
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.
Single Intervention 1
Combination of HiCO2-AIH+ Sham stimulation paired respiratory exercise
Active Comparator: Single Intervention 1
Acute intermittent hypercapnic-hypoxia (15 episodes of 1.5 minute O2= 9%, CO2=4% and balance N2, interspaced with 1.5 min room air
Respiratory Resistance Exercise
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.
Single Intervention 2
Combination of Sham Exposure + tSCS paired respiratory exercise
Active Comparator: Single Intervention 2
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.
Respiratory Resistance Exercise
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.
Sham Intervention
Combination of Sham Exposure + Sham Stimulation paired respiratory exercise
Respiratory Resistance Exercise
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.
Interventions
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Active Comparator: Single Intervention 1
Acute intermittent hypercapnic-hypoxia (15 episodes of 1.5 minute O2= 9%, CO2=4% and balance N2, interspaced with 1.5 min room air
Active Comparator: Single Intervention 2
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.
Respiratory Resistance Exercise
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. chronic SCI for ≥ 1 year at or below C-3 to T-8
3. incomplete SCI based on classification of incomplete-B, C or D
4. medically stable with clearance from physician
5. SCI due to non-progressive etiology
6. \>20% impairment in maximal inspiratory or expiratory pressure generation
Exclusion Criteria
18 Years
70 Years
ALL
No
Sponsors
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Thomas Jefferson University
OTHER
Responsible Party
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Jayakrishnan Nair
Assistant Professor
Principal Investigators
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Jay Nair, PT, PhD
Role: PRINCIPAL_INVESTIGATOR
Thomas Jefferson University
Locations
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Thomas Jefferson University Center City Campus
Philadelphia, Pennsylvania, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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1349389
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
IRBID-2023-1796
Identifier Type: -
Identifier Source: org_study_id
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