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Spinal Cord InjuriesBO2STNCT05563103

Combination Therapy to Improve SCI Recovery.

A study testing Daily acute intermittent hypoxia and Walking + tSTIM in people with Spinal Cord Injuries, run by Spaulding Rehabilitation Hospital at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to determine how combining bouts of low oxygen, transcutaneous spinal cord stimulation, and walking training may improve walking function for people with chronic spinal cord injury. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Spinal Cord Injuries
What is being tested?
Daily acute intermittent hypoxia and Walking + tSTIM
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
2 sitesUnited States
Study dates
17 Jan 2023to Dec 2026
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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 to 70 years of age
  • medically stable with medical clearance from study physician to participate
  • SCI at or below C2 (phrenic sparing) and at or above L2 with at least some sensory or motor function preserved below the neurologic level
  • non-progressive etiology of spinal injury
  • American Spinal Injury Association (ASIA) scores of C-D at initial screen
  • ambulatory (able to complete the 10-meter walk test without support from another person)
  • chronic injury (define as > 12 months post-injury) to avoid potential for spontaneous neurological plasticity and recovery

Who cannot join

  • severe concurrent illness or pain, including unhealed decubiti, severe neuropathic or chronic pain syndrome, severe infection (e.g., urinary tract), hypertension, cardiovascular disease, pulmonary disease, severe osteoporosis, active heterotopic ossification in the lower extremities, severe systemic inflammation
  • < 24 on Mini-Mental Exam
  • severe recurrent autonomic dysreflexia
  • history of severe cardiovascular/pulmonary complications including hypertension (systolic blood pressure > 150 mmHg)
  • pregnancy because of unknown effects of AIH or tSTIM on a fetus (individuals of childbearing potential will not otherwise be excluded)
  • botulinum toxin injections in lower extremity muscles within the prior three months
Show all 11Show fewer
  • history of tendon or nerve transfer surgery in the lower extremity
  • untreated severe sleep-disordered breathing characterized by uncontrolled hypoxia and sleep fractionation that may impact the outcome of this study.
  • active implanted devices (e.g., intrathecal baclofen pump)
  • receiving concurrent electrical stimulation
  • motor threshold evoked by transcutaneous spinal stimulation >200 mA

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Noah Piazza, BS contact

617-952-6953

npiazza2@mgb.org

Randy Trumbower, PT, PhD contact

randy.trumbower@mgh.harvard.edu

United States2 sites, 2 recruiting

  • Spaulding Rehabilitation Hospital

    Cambridge, Massachusetts, 02138

    Noah C Piazza, BS, 6179526822, npiazza2@mgb.org

    Randy Trumbower, PT, PhD

    Recruiting

  • Shirley Ryan AbilityLab

    Chicago, Illinois, 60611

    Shreya Aalla, BS, 312-238-7323, saalla@sralab.org

    Sara Prokup, PT, DPT, 312-238-1355, sprokup@ricres.org

    Recruiting

Other trials in United States

About this study

Official title: Breathing Low Oxygen to Enhance Spinal Stimulation Training and Functional Recovery in Persons With Chronic SCI: The BO2ST Trial

The purpose of this study is to determine how combining bouts of low oxygen, transcutaneous spinal cord stimulation, and walking training may improve walking function for people with chronic spinal cord injury.

Read the detailed description

The goal of the study is to determine whether repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) combined with transcutaneous spinal cord stimulation (tSTIM) improves recovery of walking and strength after spinal cord injury. This idea stems from animal studies on respiration, in which investigators showed that mild AIH improves breathing in rats with spinal injuries as well as studies involving spinal cord stimulation. These studies showed that AIH induces plasticity, strengthening neural connections by increasing the production of key proteins and improving the sensitivity of spinal cord circuitry. Additional studies have shown that tSTIM may enhance function and strength for people with spinal cord injuries. The ultimate goal of this research is to assess if combining AIH and tSTIM with walking training can enhance individuals walking training greater than just AIH or tSTIM. By using low oxygen as a pre-treatment to tSTIM during walking training, functional independence and quality of life for servicemen and civilians may improve.

Being tested
Daily acute intermittent hypoxia, Room air (SHAM), Walking + tSTIM, Walking + Sham transcutaneous spinal stimulation (tSHAM)
Keywords
Walk, Rehabilitation, Strength, Movement, Spinal cord injury, low oxygen, electrical stimulation, walking training
Medical subject headings
Spinal Cord Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daily acute intermittent hypoxiaOther

    Each participant will be exposed to 8 sessions of daily acute intermittent hypoxia via air generators over the span of two weeks. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02).

  • Room air (SHAM)Other

    Each participant will be exposed to 8 sessions of daily room air via air generators over the span of two weeks. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02).

  • Walking + tSTIMOther

    Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.

  • Walking + Sham transcutaneous spinal stimulation (tSHAM)Other

    Individuals will participate in 45 minutes of gait training while having SHAM transcutaneous spinal cord stimulation. The stimulation will briefly increase to 80% involuntary motor threshold and then brought down to 0 within 30 seconds.

Study groups in NCT05563103
Study groupRoleWhat they receive
AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)ExperimentalAcute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
Receives: Other: Daily acute intermittent hypoxia; Other: Walking + tSTIM
Sham + WALKtSTIMSham comparatorSham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
Receives: Other: Room air (SHAM); Other: Walking + tSTIM
AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)Sham comparatorAcute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.
Receives: Other: Daily acute intermittent hypoxia; Other: Walking + Sham transcutaneous spinal stimulation (tSHAM)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in walking recovery, assessed by 10 meter walk test (10MWT)

    Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

    Measured: Through study completion, an average of 12 weeks

  2. Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)

    Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Rate of change is the number of treatment sessions required to achieve an increase in 10MWT speed of at least the minimal clinically important difference (0.06 m/s) as compared to pre-treatment baseline.

    Measured: Through study completion, an average of 12 weeks

Secondary outcomes (6)

  1. Change in walking recovery, assessed by 6 minute walk test (6MWT)

    Participants perform the 6MWT at their fastest, most comfortable walking speed sustainable for 6 minutes. Distances will be recorded at 2 and 6 minutes. The test will be based upon the participant's ability to finish each assessment without human assistance. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

    Measured: Through study completion, an average of 12 weeks

  2. Change in walking recovery, assessed by timed up-and-go (TUG) test

    The TUG test is used to assess the dynamic balance of an individual. It measures the amount of time (recorded in seconds) it takes for the individual to rise from a standard arm chair, walk a distance of 3 meters and return to the initial position resting against the back of the chair. Participants will perform up to three trials of the TUG test. Average speed across TUG trials will be used for analysis. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

    Measured: Through study completion, an average of 12 weeks

  3. Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)

    Participants will report their pain level using the Numeric Pain Rating Scale. The scale is from 0 to 10; 0 being no pain and 10 being extreme pain. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

    Measured: Through study completion, an average of 12 weeks

  4. Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)

    The CVLT is a brief, individually administered battery to measure cognitive decline or improvement and assesses verbal learning and memory for older adolescents and adults. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

    Measured: Through treatment completion, an average of 4 weeks

  5. Systemic hypertension incidence rate

    Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140 mmHg and/or diastolic pressure exceeding 90 mmHg. A hypertension incident rate is the number of hypertensive events divided by the total person-time. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event.

    Measured: Through treatment completion, an average of 4 weeks

  6. Autonomic dysreflexia incidence rate

    The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant having a SBP increase from baseline of 20 mmHg not associated with exercise or systolic blood pressure (SBP) greater than 150 mmHg with complaints of headache, diaphoresis, and/or blurred vision and will be diagnosed by our study team clinicians. We will compute autonomic dysreflexia incident rate as the number of autonomic dysreflexia events divided by the total person-time. We define person-time in units of person-days (the number of days a person remains in the study). Person-days account for the total number of chances for detecting autonomic dysreflexia and accounts for days on which measurements were not made due to drop-out or a disqualifying adverse event.

    Measured: Through treatment completion, an average of 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2022
  2. Study start17 Jan 2023
  3. Primary completionOct 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

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
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05563103
Sponsor's protocol ID
2022P002036
Other IDs
W81XWH-22-1-0998
Acronym
BO2ST
Status last verified
Mar 2026
First submitted
26 Sep 2022
Last updated
20 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Deidentified IPD will be available to other researchers upon request.

Publications

  • Cutler MJ, Swift NM, Keller DM, Wasmund WL, Smith ML. Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea. J Appl Physiol (1985). 2004 Feb;96(2):754-61. doi: 10.1152/japplphysiol.00506.2003. Epub 2003 Oct 10.

    PubMed 14555683

  • Dale-Nagle EA, Hoffman MS, MacFarlane PM, Mitchell GS. Multiple pathways to long-lasting phrenic motor facilitation. Adv Exp Med Biol. 2010;669:225-30. doi: 10.1007/978-1-4419-5692-7_45.

    PubMed 20217354

  • Estes S, Zarkou A, Hope JM, Suri C, Field-Fote EC. Combined Transcutaneous Spinal Stimulation and Locomotor Training to Improve Walking Function and Reduce Spasticity in Subacute Spinal Cord Injury: A Randomized Study of Clinical Feasibility and Efficacy. J Clin Med. 2021 Mar 11;10(6):1167. doi: 10.3390/jcm10061167.

    PubMed 33799508

  • Gad P, Hastings S, Zhong H, Seth G, Kandhari S, Edgerton VR. Transcutaneous Spinal Neuromodulation Reorganizes Neural Networks in Patients with Cerebral Palsy. Neurotherapeutics. 2021 Jul;18(3):1953-1962. doi: 10.1007/s13311-021-01087-6. Epub 2021 Jul 9.

    PubMed 34244928

  • Tan AQ, Sohn WJ, Naidu A, Trumbower RD. Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury. Exp Neurol. 2021 Jun;340:113669. doi: 10.1016/j.expneurol.2021.113669. Epub 2021 Feb 27.

    PubMed 33647273

  • Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.

    PubMed 24285617

  • Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.

    PubMed 21821826

  • Muter WM, Mansson L, Tuthill C, Aalla S, Barth S, Evans E, McKenzie K, Prokup S, Yang C, Sandhu M, Rymer WZ, Edgerton VR, Gad P, Mitchell GS, Wu SS, Shan G, Jayaraman A, Trumbower RD. A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial. Neurotrauma Rep. 2023 Nov 6;4(1):736-750. doi: 10.1089/neur.2023.0036. eCollection 2023.

    PubMed 38028272

Questions about this trial

What is this clinical trial studying?

A study testing Daily acute intermittent hypoxia and Walking + tSTIM in people with Spinal Cord Injuries, run by Spaulding Rehabilitation Hospital at 2 sites 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 7 inclusion and 11 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 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 Noah Piazza, BS (617-952-6953, npiazza2@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in walking recovery, assessed by 10 meter walk test (10MWT) (time frame: Through study completion, an average of 12 weeks). 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 NCT05563103, which also lists 8 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 20 Mar 2026.

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