Examining the Effect of Acute Intermittent Hypoxia on Serum Blood Proteins, Corticospinal Excitability, and Force Control in Persons With Incomplete Spinal Cord Injury
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Change in Serum Blood Brain Derived Neurotrophic Factor
Study Overview
Brief Summary
The goal of this study is to clarify mechanisms of acute intermittent hypoxia and to examine the effect on lower limb function in persons with chronic, incomplete spinal cord injury.
Detailed Description
The goal of this study is to clarify mechanisms of acute intermittent hypoxia by examining changes in blood biomarkers, neural excitability, and hemoglobin mass. We also aim to clarify how these changes relate to changes in lower limb function in persons with chronic, incomplete spinal cord injury by measuring force steadiness and voluntary muscle activation.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •18 to 75 years old (the latter to reduce likelihood of heart disease)
- •Medically stable with medical clearance from physician to participate
- •Motor-incomplete spinal cord injuries at or below C2 and at or above L5
- •AIS A-D at initial screen, or other non-traumatic spinal cord injury disorders (e.g. multiple sclerosis, ALS, tumors, acute transverse myelitis, etc.)
- •More than 1 year since iSCI to minimize confounds of spontaneous neurological recovery
- •Ability to advance one step overground with or without assistive devices;
Exclusion Criteria
- •Severe concurrent illness or pain
- •Recurrent autonomic dysreflexia
- •History of cardiovascular/pulmonary complications
- •Concurrent physical therapy
- •Pregnant at time of enrollment or planning to become pregnant
- •Untreated painful musculoskeletal dysfunction, fracture or pressure sore
- •History of seizures or epilepsy
- •Recurring headaches
- •Concussion within the last six months
- •Depression or manic disorder
- •Metal implants in the head, or pacemaker
- •Aversion to needles
Arms & Interventions
AIH Group
Participants will be exposed to 4 consecutive days of acute intermittent hypoxia (AIH): 15, 1.5 min episodes at 9% O2 alternating with 21% O2 at 1 min intervals.
Intervention: Acute Intermittent Hypoxia (AIH) (Other)
SHAM Group
Participants will be exposed to 4 consecutive days of normoxia: 15, 1.5 min episodes at 21% O2 alternating with 21% O2 at 1 min intervals.
Outcomes
Primary Outcomes
Change in Serum Blood Brain Derived Neurotrophic Factor
Time Frame: Baseline, Day 1, Day 3, and Day 4
Serum blood brain derived neurotrophic factor (pg/mL) will be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.
Change in Serum Serotonin
Time Frame: Baseline, Day 1, Day 3, and Day 4
Serum serotonin (ng/mL) be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.
Change in the Transcranial Magnetic Stimulation Recruitment Curve Slope
Time Frame: Baseline and Day 4
The mean motor evoked potential response will be plotted against the corresponding stimulation intensity (% resting motor threshold) to produce a stimulus-response curve at 20% and 40% of maximum. We will measure TMS before the start of 4 consecutive days of AIH exposure. We will measure TMS within 24 hours of the final AIH exposure.
Change in Force Steadiness
Time Frame: Baseline and Day 4
The coefficient of variation of force will be calculated in both plantarflexion and dorsiflexion at 20% and 40% of maximum. We will measure coefficient of variation of force before the start of 4 consecutive days of AIH exposure. We will measure coefficient of variation of force within 24 hours of the final AIH exposure.
Change in Central Activation Ratio
Time Frame: Baseline and Day 4
We will measure the central activation ratio using supramaximal electrical stimulus over a peripheral nerve during maximum voluntary activation. We will measure the central activation ratio before the start of 4 consecutive days of AIH exposure. We will measure the central activation ratio within 24 hours of the final AIH exposure.
Change in hemoglobin mass
Time Frame: Baseline and Day 4
Using the optimized carbon monoxide rebreathing procedure we will evaluate hemoglobin concentration, carboxyhemoglobin, and hematocrit to calculate total hemoglobin mass, blood volume, and plasma volume. The optimized carbon monoxide rebreathing procedure will be done prior to the first hypoxia exposure and following the 4th hypoxia exposure.
Change in Serum Erythropoetin
Time Frame: Baseline, Day 1, Day 3, and Day 4
Serum erythropoetin (mU/mL) will be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.
Secondary Outcomes
- Axial damage ratio(Baseline)
- 6-Minute Walk Test(Baseline and Day 4)
- 10-Meter Walk Test(Baseline and Day 4)
Investigators
Andrew Quesada Tan
Assistant Professor
University of Colorado, Boulder