Spinal Cord Injuries
Conditions
Keywords
hypoxia, spinal cord injury, rehabilitation, function, low oxygen
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.
Interventions
Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.10±0.02 (hypoxia). Participants will receive treatment 4 times per week.
Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.21±0.02 (normoxia). Participants will receive treatment 4 times per week.
DEVICETESS - Transcutaneous Electrical Spinal Cord Stimulation + Functional Task Practice
Participants will receive transcutaneous electrical stimulation to the cervical spinal cord using the TESCoN device developed by SpineX, Inc. Training will consist of progressive functional task practice for upper extremity motor training. A total of 24 treatment sessions, which will last 45 minutes per session, will be completed in 3 weeks (4 days/week) per crossover arm.
Sponsors
Spaulding Rehabilitation Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Upper Extremity Function | Once each intervention week (days 5, 10, and 15), and once at follow-up (week 8) | Change compared to baseline in upper extremity function performance metrics after treatment assessed using the Graded Redefined Assessment of Strength, Sensation and Prehension test (GRASSP v2). Range: -188 to 188. Higher values represent a better outcome. |
| Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Once each intervention week (days 5, 10, and 15), and once at followup (week 8) | Change in upper extremity strength compared to baseline assessed using dynamometers to measure grip forces. |
| Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Once each intervention week (days 5, 10, and 15), and once at followup (week 8) | Change in upper extremity strength compared to baseline assessed using dynamometers to measure grip forces. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First Round 1 First Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice alone for 45 mins.
Round 1 Second Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after AIH (15x 1.5 mins bouts of 10% oxygen with 1 min intervals of room air).
Round 1 Third Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after SHAM (15x 1.5 mins bouts of 21% oxygen with 1 min intervals of room air).
Washout (1 month)
Round 2 First Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice alone for 45 mins.
Round 2 Second Intervention (4 days):Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after SHAM (15x 1.5 mins bouts of 21% oxygen with 1 min intervals of room air).
Round 2 Third Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after AIH (15x 1.5 mins bouts of 10% oxygen with 1 min intervals of room air). | 1 |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First Round 1 First Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice alone for 45 mins.
Round 1 Second Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after SHAM (15x 1.5 mins bouts of 21% oxygen with 1 min intervals of room air).
Round 1 Third Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after AIH (15x 1.5 mins bouts of 10% oxygen with 1 min intervals of room air).
Washout (1 month)
Round 2 First Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice alone for 45 mins.
Round 2 Second Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after AIH (15x 1.5 mins bouts of 10% oxygen with 1 min intervals of room air).
Round 2 Third Intervention (4 days): Participants receive 4 consecutive days of TESS during functional task practice for 45 mins after SHAM (15x 1.5 mins bouts of 21% oxygen with 1 min intervals of room air). | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Total | Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Upper Extremity Function Round 1 | 39 units on a scale | 74.7 units on a scale | 91 units on a scale |
| Upper Extremity Function Round 2 | 47 units on a scale | 76 units on a scale | 90.5 units on a scale |
| Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand Round 1 Baseline | 3.5 kg | 10.7 kg | 14.3 kg |
| Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand Round 2 Baseline | 3.6 kg | 12.8 kg | 17.45 kg |
| Upper Extremity Strength - Cylindrical Grip - More Impaired Hand Round 1 Baseline | 0 kg | 8.5 kg | 12.7 kg |
| Upper Extremity Strength - Cylindrical Grip - More Impaired Hand Round 2 Baseline | 0 kg | 10.0 kg | 15.1 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 0 / 2 | 1 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Change in Upper Extremity Function
Change compared to baseline in upper extremity function performance metrics after treatment assessed using the Graded Redefined Assessment of Strength, Sensation and Prehension test (GRASSP v2). Range: -188 to 188. Higher values represent a better outcome.
Time frame: Once each intervention week (days 5, 10, and 15), and once at follow-up (week 8)
Population: 1 subject from SHAM+TESS First group dropped out after round 2 day 5.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Day 5 | -2 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1Day 10 | 5 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Day 15 | 6 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Week 8 | 8 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 5 | -1 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 10 | 1 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 15 | -2 score on a scale |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Week 8 | 0 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Week 8 | 16 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Day 5 | 6 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 5 | 11.5 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1Day 10 | 7 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 15 | 17 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Day 15 | 7 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 2 Day 10 | 18 score on a scale |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Function | Round 1 Week 8 | -0.5 score on a scale |
Primary
Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand
Change in upper extremity strength compared to baseline assessed using dynamometers to measure grip forces.
Time frame: Once each intervention week (days 5, 10, and 15), and once at followup (week 8)
Population: 1 subject from SHAM+TESS First group dropped out after round 2 day 5.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 5 | -.47 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 10 | -.63 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 15 | -.33 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Week 8 | .10 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 5 | -.13 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 10 | .63 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 15 | .47 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Week 8 | .50 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Week 8 | -0.10 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 5 | 1.65 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 5 | 0.68 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 10 | 1.63 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 15 | -0.43 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Day 15 | 2.63 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 2 Day 10 | 1.53 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - Less Impaired Hand | Round 1 Week 8 | 3.13 kg |
Primary
Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand
Change in upper extremity strength compared to baseline assessed using dynamometers to measure grip forces.
Time frame: Once each intervention week (days 5, 10, and 15), and once at followup (week 8)
Population: 1 subject from SHAM+TESS First group dropped out after round 2 day 5.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 5 | 0 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 10 | 0 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 15 | .17 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Week 8 | 0 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 5 | 0 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 10 | 0 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 15 | .17 kg |
| Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Week 8 | 0 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Week 8 | 1.37 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 5 | 0.98 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 5 | -2.28 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 10 | 0.30 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 15 | 2.40 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Day 15 | 0.77 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 2 Day 10 | 0.27 kg |
| Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS) First | Change in Upper Extremity Strength - Cylindrical Grip - More Impaired Hand | Round 1 Week 8 | 2.35 kg |