Inspiratory Strength Training (IST)REHAB-MVNCT07427121
Rehab and Mechanical Ventilation
A study testing Spinal cord stimulation and Inspiratory Strength Training in people with Inspiratory Strength Training (IST) and Transcutaneous Spinal Stimulation, run by University of Florida at 1 site in United States.
Trial summary
The goal of this research study is to evaluate the effects of a single session of rehabilitation in healthy adults, before noninvasive mechanical ventilation (MV). MV can help support breathing function during sleep or illness. Read more about this study
- Who is it for?
- Ages 25 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Inspiratory Strength Training (IST), Transcutaneous Spinal Stimulation, Sham Spinal Stimulation
- What is being tested?
- Spinal cord stimulation and Inspiratory Strength Training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2026to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Non-smokers Sedentary or recreationally active Normal lung function No history of claustrophobia
Who cannot join
- Current smoking or vaping Obstructive lung disease Use of antibiotics or systemic corticosteroids to treat an acute condition History of sepsis or metastatic disease Post infectious conditions that affect breathing Diagnosed with a neurological or neuromuscular condition Any use of supplemental oxygen, continuous positive airway pressure (CPAP), or other positive pressure ventilation to treat sleep apnea Cardiac disease Orthopedic conditions that impair lung expansion Pregnancy Implanted metallic devices within 10 cm of the cervical spine
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Florida
Gainesville, Florida, 32610
Barbara K. Smith, PhD, 352-294-5315, bksmith@phhp.ufl.edu
Ushna Khan, MD, 352-294-5315, ushnakhan@phhp.edu
About this study
Official title: Rehabilitation-based Approaches to Prevent Mechanical Ventilation-induced Breathing Dysfunction
The goal of this research study is to evaluate the effects of a single session of rehabilitation in healthy adults, before noninvasive mechanical ventilation (MV). MV can help support breathing function during sleep or illness. High levels of MV support have been reported to alter the function of the diaphragm muscle, the primary breathing muscle, in people with compromised health. However, rehabilitation may have some potential to improve diaphragm function in advance of using MV. This study will test different rehabilitation interventions, including (1) inspiratory strength training (IST), (2) transcutaneous spinal cord stimulation (TSCS), or sham TSCS. Before and after MV, participants will complete breathing strength tests and responses to phrenic nerve stimulation.
Read the detailed description
Brief periods of mechanical ventilation (MV) can degrade the function of the diaphragm, which can be a problem for older adults and people with multiple medical comorbidities. 20% of people who are placed on MV require a prolonged effort to wean back to independent breathing. The effects of MV on respiratory neural function are often unaddressed by typical clinical practices. Many aspects of clinical practice such as MV, anesthesia, opioid medication directly reduce respiratory neural drive and degrade diaphragm fiber contractile function, and these impairments can occur rapidly, persist after extubation, and increase the risk for postoperative pulmonary complications. These complications delay discharge, incur significant expenses, and place patients at risk for an incomplete recovery and significant morbidity. Thus, any rehabilitation strategies to preserve or improve phrenic/diaphragm motor function have the potential to expedite early post-operative mobilization and reduce the risk of complications.
Inspiratory muscle strength training (IST) is an effective rehabilitation method to strengthen the diaphragm muscle. Repetitive IST reinforces respiratory neuromuscular plasticity, induces diaphragm remodeling, and improves inspiratory strength. Bouts of high intensity inspiratory loading acutely increase respiratory neural drive and potentiates inspiratory motor recruitment. Additionally, in some clinical situations, IST exercise is not feasible, thus another option may be electrical stimulation of the diaphragm/phrenic motor area (C3-C6) to generate similar improvements in inspiratory drive to preserve breathing function.
The central hypothesis of this proposal is that rehabilitation to increase diaphragm excitability in advance of MV will offset post-MV inspiratory dysfunction. To test this hypothesis, a repeated-measures, blinded study of healthy adults without respiratory comorbidities will be recruited. Consenting participants will complete a familiarization session, followed by three separate, two-hour noninvasive MV sessions, one week apart. MV sessions will be preceded by: 1) a single, high-intensity IST session, and 2) transcutaneous spinal cord stimulation, and 3) sham electrical stimulation, in randomized order. Changes in respiratory drive, voluntary and evoked diaphragm strength, and dyspnea will be evaluated. The central hypothesis will be tested with the following aims:
Aim 1: Test the hypothesis that noninvasive, positive pressure ventilation acutely decreases respiratory drive and maximal diaphragm activation during a two-hour MV session and persists up to 24 hours later.
Aim 2: Test the hypothesis that even single rehabilitation sessions (IST, transcutaneous stimulation) in advance of MV will preserve evoked diaphragm recruitment and hasten early recovery from MV, when compared to sham stimulation.
- Conditions
- Inspiratory Strength Training (IST), Transcutaneous Spinal Stimulation, Sham Spinal Stimulation
- Being tested
- Spinal cord stimulation, Inspiratory Strength Training, Sham Stimulation
- Keywords
- diaphragm, phrenic nerve, maximal inspiratory pressure, mechanical ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spinal cord stimulationDevice
Transcutaneous spinal cord stimulation at 2mA intensity, for 20 minutes.
Inspiratory Strength TrainingBehavioural
5 sets of 5 breaths of high-intensity inspiratory strength training
Sham StimulationOther
Transcutaneous spinal cord stimulation at reduced intensity, lasting 1 minute at the beginning and end of a 20-minute session.
| Study group | Role | What they receive |
|---|---|---|
| Sham Stimulation | Sham comparator | Transcutaneous spinal cord stimulation at reduced intensity, lasting 1 minute at the beginning and end of a 20-minute session. Receives: Other: Sham Stimulation |
| Spinal cord stimulation | Active comparator | Transcutaneous spinal cord stimulation at 2mA intensity, for 20 minutes. Receives: Device: Spinal cord stimulation |
| Inspiratory strength training | Experimental | 5 sets of 5 breaths of high-intensity inspiratory strength training Receives: Behavioral: Inspiratory Strength Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal inspiratory pressure
The most negative pressure generated during a maximal inspiratory effort.
Measured: T1: baseline strength, T2: 2 hours after MV, T3: 24 hours after MV
Phrenic CMAP Response
EMG response to supra maximal and bilateral phrenic stimulation
Measured: up to 24 hours
Secondary outcomes (1)
Diaphragm thickness and excursion
Diaphragm thickness and excursion will be computed during resting breathing and during inspiratory efforts.
Measured: up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2026
- Study start30 Mar 2026
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Inspiratory Strength Training (IST)Studies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Barbara K Smith, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07427121
- Sponsor's protocol ID
- IRB202501849
- Acronym
- REHAB-MV
- Status last verified
- Apr 2026
- First submitted
- 17 Feb 2026
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Participant data that underlie the results reported in this article after deidentification.
Publications
Ando R, Ohya T, Kusanagi K, Koizumi J, Ohnuma H, Katayama K, Suzuki Y. Effect of inspiratory resistive training on diaphragm shear modulus and accessory inspiratory muscle activation. Appl Physiol Nutr Metab. 2020 Aug;45(8):851-856. doi: 10.1139/apnm-2019-0906. Epub 2020 Feb 12.
PubMed 32049562Laghi F, Shaikh H, Littleton SW, Morales D, Jubran A, Tobin MJ. Inhibition of central activation of the diaphragm: a mechanism of weaning failure. J Appl Physiol (1985). 2020 Aug 1;129(2):366-376. doi: 10.1152/japplphysiol.00856.2019. Epub 2020 Jul 16.
PubMed 32673161Nierat MC, Similowski T, Lamy JC. Does trans-spinal direct current stimulation alter phrenic motoneurons and respiratory neuromechanical outputs in humans? A double-blind, sham-controlled, randomized, crossover study. J Neurosci. 2014 Oct 22;34(43):14420-9. doi: 10.1523/JNEUROSCI.1288-14.2014.
PubMed 25339753Locher C, Raux M, Fiamma MN, Morelot-Panzini C, Zelter M, Derenne JP, Similowski T, Straus C. Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans. BMC Physiol. 2006 Jul 29;6:7. doi: 10.1186/1472-6793-6-7.
PubMed 16875504Hawkes EZ, Nowicky AV, McConnell AK. Diaphragm and intercostal surface EMG and muscle performance after acute inspiratory muscle loading. Respir Physiol Neurobiol. 2007 Mar 15;155(3):213-9. doi: 10.1016/j.resp.2006.06.002. Epub 2006 Jul 18.
PubMed 16846758Fauroux B, Isabey D, Desmarais G, Brochard L, Harf A, Lofaso F. Nonchemical influence of inspiratory pressure support on inspiratory activity in humans. J Appl Physiol (1985). 1998 Dec;85(6):2169-75. doi: 10.1152/jappl.1998.85.6.2169.
PubMed 9843540Bresciani G, Beaver T, Martin AD, van der Pijl R, Mankowski R, Leeuwenburgh C, Ottenheijm CAC, Martin T, Arnaoutakis G, Ahmed S, Mariani VM, Xue W, Smith BK, Ferreira LF. Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery. PLoS One. 2025 Apr 1;20(4):e0320936. doi: 10.1371/journal.pone.0320936. eCollection 2025.
PubMed 40168300
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rehabilitation-based Approaches to Prevent Mechanical Ventilation-induced Breathing Dysfunction
- ClinicalTrials.gov ID
- NCT07427121
- Acronym / sponsor ID
- REHAB-MV / IRB202501849
- Conditions
- Inspiratory Strength Training (IST), Transcutaneous Spinal Stimulation, Sham Spinal Stimulation
- Keywords
- diaphragm, phrenic nerve, maximal inspiratory pressure, mechanical ventilation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 30 Mar 2026 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 23 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this research study is to evaluate the effects of a single session of rehabilitation in healthy adults, before noninvasive mechanical ventilation (MV). MV can help support breathing function during sleep or illness. High levels of MV support have been reported to alter the function of the diaphragm muscle, the primary breathing muscle, in people with compromised health. However, rehabilitation may have some potential to improve diaphragm function in advance of using MV. This study will test different rehabilitation interventions, including (1) inspiratory strength training (IST), (2) transcutaneous spinal cord stimulation (TSCS), or sham TSCS. Before and after MV, participants will complete breathing strength tests and responses to phrenic nerve stimulation.
Detailed description
Brief periods of mechanical ventilation (MV) can degrade the function of the diaphragm, which can be a problem for older adults and people with multiple medical comorbidities. 20% of people who are placed on MV require a prolonged effort to wean back to independent breathing. The effects of MV on respiratory neural function are often unaddressed by typical clinical practices. Many aspects of clinical practice such as MV, anesthesia, opioid medication directly reduce respiratory neural drive and degrade diaphragm fiber contractile function, and these impairments can occur rapidly, persist after extubation, and increase the risk for postoperative pulmonary complications. These complications delay discharge, incur significant expenses, and place patients at risk for an incomplete recovery and significant morbidity. Thus, any rehabilitation strategies to preserve or improve phrenic/diaphragm motor function have the potential to expedite early post-operative mobilization and reduce the risk of complications.
Inspiratory muscle strength training (IST) is an effective rehabilitation method to strengthen the diaphragm muscle. Repetitive IST reinforces respiratory neuromuscular plasticity, induces diaphragm remodeling, and improves inspiratory strength. Bouts of high intensity inspiratory loading acutely increase respiratory neural drive and potentiates inspiratory motor recruitment. Additionally, in some clinical situations, IST exercise is not feasible, thus another option may be electrical stimulation of the diaphragm/phrenic motor area (C3-C6) to generate similar improvements in inspiratory drive to preserve breathing function.
The central hypothesis of this proposal is that rehabilitation to increase diaphragm excitability in advance of MV will offset post-MV inspiratory dysfunction. To test this hypothesis, a repeated-measures, blinded study of healthy adults without respiratory comorbidities will be recruited. Consenting participants will complete a familiarization session, followed by three separate, two-hour noninvasive MV sessions, one week apart. MV sessions will be preceded by: 1) a single, high-intensity IST session, and 2) transcutaneous spinal cord stimulation, and 3) sham electrical stimulation, in randomized order. Changes in respiratory drive, voluntary and evoked diaphragm strength, and dyspnea will be evaluated. The central hypothesis will be tested with the following aims:
Aim 1: Test the hypothesis that noninvasive, positive pressure ventilation acutely decreases respiratory drive and maximal diaphragm activation during a two-hour MV session and persists up to 24 hours later.
Aim 2: Test the hypothesis that even single rehabilitation sessions (IST, transcutaneous stimulation) in advance of MV will preserve evoked diaphragm recruitment and hasten early recovery from MV, when compared to sham stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sham Stimulation | Sham comparator | Other: Sham StimulationTranscutaneous spinal cord stimulation at reduced intensity, lasting 1 minute at the beginning and end of a 20-minute session. |
| Spinal cord stimulation | Active comparator | Device: Spinal cord stimulationTranscutaneous spinal cord stimulation at 2mA intensity, for 20 minutes. |
| Inspiratory strength training | Experimental | Behavioral: Inspiratory Strength Training5 sets of 5 breaths of high-intensity inspiratory strength training |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Non-smokers Sedentary or recreationally active Normal lung function No history of claustrophobia
Key exclusion criteria (1 listed)
- Current smoking or vaping Obstructive lung disease Use of antibiotics or systemic corticosteroids to treat an acute condition History of sepsis or metastatic disease Post infectious conditions that affect breathing Diagnosed with a neurological or neuromuscular condition Any use of supplemental oxygen, continuous positive airway pressure (CPAP), or other positive pressure ventilation to treat sleep apnea Cardiac disease Orthopedic conditions that impair lung expansion Pregnancy Implanted metallic devices within 10 cm of the cervical spine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spinal cord stimulationTranscutaneous spinal cord stimulation at 2mA intensity, for 20 minutes. | Device | Spinal cord stimulation |
| Inspiratory Strength Training5 sets of 5 breaths of high-intensity inspiratory strength training | Behavioural | Inspiratory strength training |
| Sham StimulationTranscutaneous spinal cord stimulation at reduced intensity, lasting 1 minute at the beginning and end of a 20-minute session. | Other | Sham Stimulation |
Primary outcome
Maximal inspiratory pressure
Time frame: T1: baseline strength, T2: 2 hours after MV, T3: 24 hours after MV
The most negative pressure generated during a maximal inspiratory effort.
Phrenic CMAP Response
Time frame: up to 24 hours
EMG response to supra maximal and bilateral phrenic stimulation
1 secondary outcome
Diaphragm thickness and excursion
Time frame: up to 24 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Background: PubMed 32049562Ando R, Ohya T, Kusanagi K, Koizumi J, Ohnuma H, Katayama K, Suzuki Y. Effect of inspiratory resistive training on diaphragm shear modulus and accessory inspiratory muscle activation. Appl Physiol Nutr Metab. 2020 Aug;45(8):851-856. doi: 10.1139/apnm-2019-0906. Epub 2020 Feb 12.
- Background: PubMed 32673161Laghi F, Shaikh H, Littleton SW, Morales D, Jubran A, Tobin MJ. Inhibition of central activation of the diaphragm: a mechanism of weaning failure. J Appl Physiol (1985). 2020 Aug 1;129(2):366-376. doi: 10.1152/japplphysiol.00856.2019. Epub 2020 Jul 16.
- Background: PubMed 25339753Nierat MC, Similowski T, Lamy JC. Does trans-spinal direct current stimulation alter phrenic motoneurons and respiratory neuromechanical outputs in humans? A double-blind, sham-controlled, randomized, crossover study. J Neurosci. 2014 Oct 22;34(43):14420-9. doi: 10.1523/JNEUROSCI.1288-14.2014.
- Background: PubMed 16875504Locher C, Raux M, Fiamma MN, Morelot-Panzini C, Zelter M, Derenne JP, Similowski T, Straus C. Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans. BMC Physiol. 2006 Jul 29;6:7. doi: 10.1186/1472-6793-6-7.
- Background: PubMed 16846758Hawkes EZ, Nowicky AV, McConnell AK. Diaphragm and intercostal surface EMG and muscle performance after acute inspiratory muscle loading. Respir Physiol Neurobiol. 2007 Mar 15;155(3):213-9. doi: 10.1016/j.resp.2006.06.002. Epub 2006 Jul 18.
- Background: PubMed 9843540Fauroux B, Isabey D, Desmarais G, Brochard L, Harf A, Lofaso F. Nonchemical influence of inspiratory pressure support on inspiratory activity in humans. J Appl Physiol (1985). 1998 Dec;85(6):2169-75. doi: 10.1152/jappl.1998.85.6.2169.
- Background: PubMed 40168300Bresciani G, Beaver T, Martin AD, van der Pijl R, Mankowski R, Leeuwenburgh C, Ottenheijm CAC, Martin T, Arnaoutakis G, Ahmed S, Mariani VM, Xue W, Smith BK, Ferreira LF. Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery. PLoS One. 2025 Apr 1;20(4):e0320936. doi: 10.1371/journal.pone.0320936. eCollection 2025.
- Individual participant dataSharing planned: Yes. Participant data that underlie the results reported in this article after deidentification.
Related trials for Inspiratory Strength Training (IST)
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Breathing for Two: Inspiratory Muscle Strength Training for Supporting Healthy Blood Pressure in Pregnancy
Hypertension Disorders in Pregnancy, Blood Pressure Measurement in Pregnancy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Barbara K Smith, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spinal cord stimulation and Inspiratory Strength Training in people with Inspiratory Strength Training (IST) and Transcutaneous Spinal Stimulation, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Barbara K Smith, PhD, PT (352-294-5315, bksmith@ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal inspiratory pressure (time frame: T1: baseline strength, T2: 2 hours after MV, T3: 24 hours after MV). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07427121, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.