Combination Therapy to Improve SCI Recovery. (BO2ST)

March 18, 2026 updated by: Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Shirley Ryan AbilityLab
        • Contact:
        • Contact:
        • Principal Investigator:
          • Arun Jayaraman, PT, PhD
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02138
        • Recruiting
        • Spaulding Rehabilitation Hospital
        • Principal Investigator:
          • Randy Trumbower, PT, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)
Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
Other: Daily acute intermittent hypoxia
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).
Other: Walking + tSTIM
Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.
Sham Comparator: Sham + WALKtSTIM
Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
Other: Walking + tSTIM
Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.
Other: Room air (SHAM)
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).
Sham Comparator: AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)
Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.
Other: Daily acute intermittent hypoxia
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).
Other: Walking + Sham transcutaneous spinal stimulation (tSHAM)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in walking recovery, assessed by 10 meter walk test (10MWT)
Time Frame: Through study completion, an average of 12 weeks
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.
Through study completion, an average of 12 weeks
Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)
Time Frame: Through study completion, an average of 12 weeks
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.
Through study completion, an average of 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in walking recovery, assessed by 6 minute walk test (6MWT)
Time Frame: Through study completion, an average of 12 weeks
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.
Through study completion, an average of 12 weeks
Change in walking recovery, assessed by timed up-and-go (TUG) test
Time Frame: Through study completion, an average of 12 weeks
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.
Through study completion, an average of 12 weeks
Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)
Time Frame: Through study completion, an average of 12 weeks
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.
Through study completion, an average of 12 weeks
Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)
Time Frame: Through treatment completion, an average of 4 weeks
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.
Through treatment completion, an average of 4 weeks
Systemic hypertension incidence rate
Time Frame: Through treatment completion, an average of 4 weeks
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.
Through treatment completion, an average of 4 weeks
Autonomic dysreflexia incidence rate
Time Frame: Through treatment completion, an average of 4 weeks
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.
Through treatment completion, an average of 4 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS)
Time Frame: Through study completion, an average of 12 weeks
The LEMS uses ASIA key muscles in both the lower extremities, with a total possible score of 50 (maximum score of 5 for each muscle group). Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks
Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)
Time Frame: Through study completion, an average of 12 weeks
The study team will quantify the total lower extremity spasticity score using the cumulative sum of 3 SCATS subscales: clonus (0=no spasticity; 3=severe), flexor (0=no spasticity; 3=severe), and extensor (0=no spasticity; 3=severe). Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks
Change in bladder dysfunction, assessed by the Neurogenic Bladder Symptom Score (NBSS)
Time Frame: Through study completion, an average of 12 weeks
This questionnaire is a symptom-based score for neurogenic bladder dysfunction. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks
Change in walking ability and assistive device use, assessed by Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).
Time Frame: Through study completion, an average of 12 weeks
The SCI-FAI assesses functional walking ability in ambulatory individuals with SCI. Component scores range from 0 to 20 in the gait parameter component, 0 to 14 in the assistive device component, and 0 to 5 in the walking mobility component. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks
Change in physical assistance needed, assessed by Walking Index for Spinal Cord Injury (WISCI) II
Time Frame: Through study completion, an average of 12 weeks
The WISCI is used to assess the amount of physical assistance is needed as well as devices required for walking following paralysis. This assessment is from 0-20 with value corresponding to a physical assistance description. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks
Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1
Time Frame: Through study completion, an average of 12 weeks
This questionnaire is a symptom-based score for neurogenic bowel dysfunction. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Through study completion, an average of 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spaulding Rehabilitation Hospital

Collaborators

United States Department of Defense
Shirley Ryan AbilityLab

Investigators

  • Principal Investigator: Randy Trumbower, PT, PhD, Harvard Medical School (HMS and HSDM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 26, 2022

First Submitted That Met QC Criteria

September 28, 2022

First Posted (Actual)

October 3, 2022

Study Record Updates

Last Update Posted (Actual)

March 20, 2026

Last Update Submitted That Met QC Criteria

March 18, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022P002036
  • W81XWH-22-1-0998 (Other Grant/Funding Number: US Dept. of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified IPD will be available to other researchers upon request.

IPD Sharing Time Frame

The study protocol and statistical analysis plan will be disseminated by December 2022. Participant data will be available at the end of the trial.

IPD Sharing Access Criteria

Principal investigators will be able to receive deidentified data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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