Combination Therapy to Improve SCI Recovery.

Not Applicable

Recruiting

• Conditions: Spinal Cord Injuries
• Interventions: Other: Daily acute intermittent hypoxia; Other: Room air (SHAM); Other: Walking + tSTIM; Other: Walking + Sham transcutaneous spinal stimulation (tSHAM)

• Registration Number: NCT05563103
• Lead Sponsor: Spaulding Rehabilitation Hospital

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.

Study Timeline

• Study First Submitted: 2022-09-26
• Study First Submitted QC: 2022-09-28
• Study First Posted: 2022-10-03
• Study Start: 2023-01-17
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-10
• Last Update Posted: 2024-07-12
• Primary Completion: 2026-10
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham + WALKtSTIM	Walking + tSTIM	Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)	Walking + tSTIM	Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)	Walking + Sham transcutaneous spinal stimulation (tSHAM)	Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.
AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)	Daily acute intermittent hypoxia	Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
Sham + WALKtSTIM	Room air (SHAM)	Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.
AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)	Daily acute intermittent hypoxia	Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.

Primary Outcome Measures

Name	Time	Method
Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)	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.
Change in walking recovery, assessed by 10 meter walk test (10MWT)	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.

Secondary Outcome Measures

Name	Time	Method
Change in walking recovery, assessed by 6 minute walk test (6MWT)	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.
Change in walking recovery, assessed by timed up-and-go (TUG) test	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.
Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)	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.
Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)	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.
Systemic hypertension incidence rate	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.
Autonomic dysreflexia incidence rate	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.

Trial Locations

Locations (2)

Shirley Ryan AbilityLab; 🇺🇸 Chicago, Illinois, United States

Spaulding Rehabilitation Hospital; 🇺🇸 Cambridge, Massachusetts, United States