Combination Therapy to Improve SCI Recovery. (BO2ST)

Mass General Brigham

Status: Enrolling

Conditions: Spinal Cord Injuries

Treatments: Other: Daily acute intermittent hypoxia; Other: Walking + Sham transcutaneous spinal stimulation (tSHAM); Other: Room air (SHAM); Other: Walking + tSTIM

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT05563103

2022P002036

W81XWH-22-1-0998 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 3 patient groups

AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)

Experimental group

Description:

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

Treatment:

Other: Walking + tSTIM

Other: Daily acute intermittent hypoxia

Sham + WALKtSTIM

Sham Comparator group

Description:

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

Treatment:

Other: Walking + tSTIM

Other: Room air (SHAM)

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

Sham Comparator group

Description:

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

Treatment:

Other: Walking + Sham transcutaneous spinal stimulation (tSHAM)

Other: Daily acute intermittent hypoxia