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Combination Therapy to Improve SCI Recovery. (BO2ST)

Primary Purpose

Spinal Cord Injuries

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Daily acute intermittent hypoxia

Room air (SHAM)

Walking + tSTIM

Walking + Sham transcutaneous spinal stimulation (tSHAM)

About this trial

This is an interventional treatment trial for Spinal Cord Injuries focused on measuring Walk, Rehabilitation, Strength, Movement, Spinal cord injury, low oxygen, electrical stimulation, walking training

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 six 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

Sites / Locations

Shirley Ryan AbilityLabRecruiting
Spaulding Rehabilitation HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Sham Comparator

Arm Label

AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)

Sham + WALKtSTIM

AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)

Arm Description

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05563103

First Posted

September 26, 2022

Last Updated

October 24, 2023

Sponsor

Spaulding Rehabilitation Hospital

Collaborators

United States Department of Defense, Shirley Ryan AbilityLab

1. Study Identification

Unique Protocol Identification Number

NCT05563103

Brief Title

Combination Therapy to Improve SCI Recovery.

Acronym

BO2ST

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 17, 2023 (Actual)

Primary Completion Date

October 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Spaulding Rehabilitation Hospital

Collaborators

United States Department of Defense, Shirley Ryan AbilityLab

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Cord Injuries

Keywords

Walk, Rehabilitation, Strength, Movement, Spinal cord injury, low oxygen, electrical stimulation, walking training

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)

Arm Type

Experimental

Arm Description

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Arm Title

Sham + WALKtSTIM

Arm Type

Sham Comparator

Arm Description

Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Arm Title

AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)

Arm Type

Sham Comparator

Arm Description

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.

Intervention Type

Other

Intervention Name(s)

Daily acute intermittent hypoxia

Intervention Description

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).

Intervention Type

Other

Intervention Name(s)

Room air (SHAM)

Intervention Description

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).

Intervention Type

Other

Intervention Name(s)

Walking + tSTIM

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Walking + Sham transcutaneous spinal stimulation (tSHAM)

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Through study completion, an average of 12 weeks

Title

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

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Through study completion, an average of 12 weeks

Title

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

Description

Time Frame

Through study completion, an average of 12 weeks

Title

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

Description

Time Frame

Through study completion, an average of 12 weeks

Title

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

Description

Time Frame

Through treatment completion, an average of 4 weeks

Title

Systemic hypertension incidence rate

Description

Time Frame

Through treatment completion, an average of 4 weeks

Title

Autonomic dysreflexia incidence rate

Description

Time Frame

Through treatment completion, an average of 4 weeks

Other Pre-specified Outcome Measures:

Title

Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS)

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Title

Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Title

Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Title

Change in bladder dysfunction, assessed by the Neurogenic Bladder Symptom Score (NBSS)

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Title

Change in walking ability and assistive device use, assessed by Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).

Description

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.

Time Frame

Through study completion, an average of 12 weeks

Title

Change in physical assistance needed, assessed by Walking Index for Spinal Cord Injury (WISCI) II

Description

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.

Time Frame

Through study completion, an average of 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 six 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

William M. Muter, BS

Phone

617-952-6953

wmuter@partners.org

First Name & Middle Initial & Last Name or Official Title & Degree

Randy Trumbower, PT, PhD

randy.trumbower@mgh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Randy Trumbower, PT, PhD

Organizational Affiliation

Harvard Medical School (HMS and HSDM)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shirley Ryan AbilityLab

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shreya Aalla, BS

Phone

312-238-7323

saalla@sralab.org

First Name & Middle Initial & Last Name & Degree

Sara Prokup, PT, DPT

Phone

312-238-1355

sprokup@ricres.org

First Name & Middle Initial & Last Name & Degree

Arun Jayaraman, PT, PhD

Facility Name

Spaulding Rehabilitation Hospital

City

Cambridge

State/Province

Massachusetts

ZIP/Postal Code

02138

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

William M Muter, BS

Phone

617-952-6953

wmuter@partners.org

First Name & Middle Initial & Last Name & Degree

Julia Gangemi, BS

jgangemi@mgh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Randy Trumbower, PT, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

14555683

Citation

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.

Results Reference

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PubMed Identifier

20217354

Citation

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.

Results Reference

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PubMed Identifier

33799508

Citation

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.

Results Reference

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PubMed Identifier

34244928

Citation

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.

Results Reference

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PubMed Identifier

33647273

Citation

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.

Results Reference

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PubMed Identifier

24285617

Citation

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.

Results Reference

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PubMed Identifier

21821826

Citation

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.

Results Reference

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Combination Therapy to Improve SCI Recovery.

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