Clinical trial NCT06521723: Low Oxygen Therapy to Enhance Walking Recovery After SCI.
Official title: Breathing Low Oxygen to Enhance Spinal Stimulation Training and Functional Recovery for Aging Adults With Chronic SCI: The BO2ST-II Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: Walk
Rehabilitation
Strength
Movement
Low oxygen
Electrical stimulation
Gait training
Lead sponsor: Spaulding Rehabilitation Hospital
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Brooks Rehabilitation
First posted: 2024-07-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 of different age groups.

Detailed description: The goal of the study is to determine the optimal dosage for different age groups of repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) combined with transcutaneous spinal cord stimulation (tSTIM) to improve recovery of walking and strength after spinal cord injury. Preliminary studies have shown that 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 may improve. Despite exciting preliminary results supporting the efficacy of AIH and tSTIM to enhance walking recovery after SCI, understanding factors that may enhance or undermine treatment responsiveness is warranted. Factors include establishing the role of age and sex dependency on appropriate dosing (number of sessions) AIH to provide the greatest plasticity-promoting effects on walking recovery for our aging population of persons living with SCI.

Eligibility criteria: Inclusion Criteria:

* 18 to 80 years of age
* medically stable with medical clearance from study physician to participate
* SCI at or below C1 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

Primary outcomes:
measure: Change in walking recovery, assessed by 10 meter walk test (10MWT)
timeFrame: Through study completion, an average of 14 weeks
measure: Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)
timeFrame: Through study completion, an average of 14 weeks
Secondary outcomes:
measure: Change in walking recovery, assessed by 6 minute walk test (6MWT)
timeFrame: Through study completion, an average of 14 weeks
measure: Change in walking recovery, assessed by timed up-and-go (TUG) test
timeFrame: Through study completion, an average of 14 weeks
measure: Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)
timeFrame: Through study completion, an average of 14 weeks
measure: Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)
timeFrame: Through treatment completion, an average of 6 weeks
measure: Counts of hypertensive events
timeFrame: Through treatment completion, an average of 6 weeks
measure: Counts of blood pressure measurements
timeFrame: Through treatment completion, an average of 6 weeks
measure: Systemic hypertension incidence rate
timeFrame: Through treatment completion, an average of 6 weeks
measure: Number of autonomic dysreflexia events
timeFrame: Through treatment completion, an average of 6 weeks
measure: Total person-time for autonomic dysreflexia
timeFrame: Through treatment completion, an average of 6 weeks
measure: Autonomic dysreflexia incidence rate
timeFrame: Through treatment completion, an average of 6 weeks
measure: Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS)
timeFrame: Through study completion, an average of 14 weeks
measure: Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)
timeFrame: Through study completion, an average of 14 weeks
measure: Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1
timeFrame: Through study completion, an average of 14 weeks
measure: Change in bladder dysfunction, assessed by the Neurogenic Bladder Symptom Score (NBSS)
timeFrame: Through study completion, an average of 14 weeks
measure: Change in walking ability and assistive device use, assessed by Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).
timeFrame: Through study completion, an average of 14 weeks
measure: Change in physical assistance needed, assessed by Walking Index for Spinal Cord Injury (WISCI) II
timeFrame: Through study completion, an average of 14 weeks
measure: Change in breathing function, assessed by FVC
timeFrame: Through study completion, an average of 14 weeks
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Brooks Rehabilitation Hospital
state: Florida
city: Cambridge
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: Randy Trumbower, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
citation: 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.