Clinical trial NCT04854057: Pairing Intermittent Hypoxia and Transcutaneous Electrical Spinal Cord Stimulation to Promote Arm Use After Cervical SCI
Official title: Combinatorial Treatment of Acute Intermittent Hypoxia and Transcutaneous Electrical Spinal Cord Stimulation to Improve Hand Function in People With Cervical Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: hypoxia
spinal cord injury
rehabilitation
function
low oxygen
Lead sponsor: Spaulding Rehabilitation Hospital
Sponsor class: OTHER
First posted: 2021-04-22
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the efficacy of mild breathing bouts of low oxygen (intermittent hypoxia) combined with transcutaneous electrical spinal cord stimulation on restoring hand function in persons with chronic incomplete spinal cord injury.

Detailed description: The goal of this study is to determine the effectiveness of repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) combined with non-invasive transcutaneous electrical spinal cord stimulation (TESS) on restoring hand function in persons with chronic incomplete SCI.

The fundamental hypothesis guiding this proposal is that daily AIH+TESS engage excitatory and inhibitory pathways, which converge on a common plasticity-promoting cascade that induces greater recovery of hand function than either one alone.

Both treatments appear to enhance motor function in persons with cervical SCI. Despite their independent effects on promoting functional benefits, it is not yet know if they may promote greater functional benefits when combined. To be effective as a long-term rehabilitation strategy, it is essential to determine the efficacy of combined protocols of recurring AIH+TESS.

Eligibility criteria: Inclusion Criteria:

* 18 to 65 years old
* medically stable with medical clearance from physician to participate
* SCI at or below C3 and at or above C7
* non-progressive etiology of spinal injury
* American Spinal Injury Association Impairment Scale (AIS) C-D at initial screen
* at least 1 year post-injury (chronic)
* difficulty independently performing hand functions in activities of daily living

Exclusion Criteria:

* dependence on ventilation support
* implanted stimulator (e.g. diaphragm pacing by phrenic nerve stimulation, vagus nerve stimulator, pacemaker, cochlear implant, epidural stimulator, baclofen pump, etc.)
* spinal cord injury related complications including unhealed pressure sore, severe neuropathic or chronic pain syndrome, history of frequent autonomic dysreflexia, infection (e.g. urinary tract), cardiovascular disease (e.g. deep vein thrombosis), pulmonary disease, heterotopic ossification in the upper extremities, severe osteoporosis, unhealed fracture, contracture of the upper extremity joints
* received botulinum toxin injections in upper extremity muscles in the prior 6 months
* history of tendon or nerve transfer surgery in the upper extremity
* history of additional neurologic disease, such as stroke, multiple sclerosis, traumatic brain injury, peripheral neuropathy (diabetic polyneuropathy, entrapment neuropathy, etc.) or peripheral nerve injury in the upper extremity
* history of concomitant diseases that would prevent full participation in intensive exercise therapy, such as uncontrolled hypertension, rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), pulmonary disease, active cancer, chronic contagious disease, etc.
* anticoagulation medication
* pregnancy
* history of allergic reaction or any skin reaction to use of adhesive electrodes

Primary outcomes:
measure: Change in Upper Extremity Function
timeFrame: Once each intervention week (days 5, 10, and 15), and once at follow-up (week 8)
measure: Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand
timeFrame: Once each intervention week (days 5, 10, and 15), and once at followup (week 8)
measure: Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand
timeFrame: Once each intervention week (days 5, 10, and 15), and once at followup (week 8)
Secondary outcomes:
Other outcomes:
Locations:
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: Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29.
citation: Inanici F, Samejima S, Gad P, Edgerton VR, Hofstetter CP, Moritz CT. Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. IEEE Trans Neural Syst Rehabil Eng. 2018 Jun;26(6):1272-1278. doi: 10.1109/TNSRE.2018.2834339.
citation: Hoffman L, Field-Fote E. Effects of practice combined with somatosensory or motor stimulation on hand function in persons with spinal cord injury. Top Spinal Cord Inj Rehabil. 2013 Fall;19(4):288-99. doi: 10.1310/sci1904-288.
citation: Gad P, Lee S, Terrafranca N, Zhong H, Turner A, Gerasimenko Y, Edgerton VR. Non-Invasive Activation of Cervical Spinal Networks after Severe Paralysis. J Neurotrauma. 2018 Sep 15;35(18):2145-2158. doi: 10.1089/neu.2017.5461.