Incomplete Spinal Cord Injury
Conditions
Keywords
Spinal Cord Injury, Motor Adaptation, Acute Intermittent Hypoxia
Brief summary
The goal of this study is to examine the effect of repetitive acute intermittent hypoxia on motor learning abilities in able-bodied individuals for subsequent study in individuals with incomplete spinal cord injury.
Interventions
5 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals
5 consecutive days of 15, 1.5 min episodes at 21% O2 (SHAM AIH) alternating with 21% O2 at 1 min intervals
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Colorado, Denver
Medical University of South Carolina
University of Colorado, Boulder
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This study design is twofold. The first study examines the effects of AIH on motor learning using an AIH group and a control group (total N = 30). The second part of this study examines corticospinal indices of motor learning using an AIH group and a SHAM group (i.e., blinded normoxia; total N = 26).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 70 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 disorders * Metal implants in the head, or pacemaker.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Corticospinal Excitability | We will measure TMS before the start of 5 consecutive days of AIH or SHAM treatment. We will measure TMS within 24 hours of the final treatment. | Transcranial magnetic stimulation (TMS) can be applied over the primary motor cortex to examine changes in corticospinal excitability. The downstream muscle activation can be recorded with surface EMG as a motor-evoked potential (MEP). The peak-to-peak MEP amplitude (mV) is as an index of corticospinal excitability. A randomized sequence of TMS intensities can be applied over the primary motor cortex, ranging from 90-140% of the participants' resting motor threshold (RMT). The mean MEP amplitude will be plotted against the corresponding stimulation intensity to produce the recruitment curve. The area under the recruitment curve is an additional index of corticospinal excitability (mV/% RMT). |
| Step Length Asymmetry | We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group). | Step length asymmetry will be quantified as the ratio of the normalized difference in step lengths between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step length) / (Fast leg + Slow leg step length). |
| Step Time Asymmetry | We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group). | Step time asymmetry will be quantified as the ratio of the normalized difference in step times between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step time) / (Fast leg + Slow leg step time). |
| Net Metabolic Power | We will compare net metabolic power 15 minutes after the final AIH treatment to asymmetry following no treatment (control group). | Using expired gas analyses, we will calculate net metabolic power by inputting steady-state values for V̇O₂ and V̇CO₂ into standard regression equations (W), subtracting resting values, and normalizing the result to each participant's body weight (kg). |
Countries
United States
Participant flow
Recruitment details
Individuals were recruited through advertisements in Colorado, with recruitment occurring from May 2022 through January 2025. A total of 56 participants were enrolled across both studies. Part 1: Motor Learning (N = 30) & Part 2: Corticospinal Indices of Motor Learning (N = 26).
Pre-assignment details
Participants were randomly assigned to their respective groups and completed either AIH, SHAM, or no treatment before undergoing motor learning assessments using a split-belt treadmill paradigm. Qualifying participants also received corticospinal excitability assessments using transcranial magnetic stimulation (TMS).
Participants by arm
| Arm | Count |
|---|---|
| Repetitive Acute Intermittent Hypoxia 5 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals | 28 |
| SHAM Acute Intermittent Hypoxia 5 consecutive days of 15, 1.5 min episodes at 21% O2 (SHAM AIH) alternating with 21% O2 at 1 min intervals | 13 |
| Control Group No AIH or SHAM exposure | 15 |
| Total | 56 |
Baseline characteristics
| Characteristic | Repetitive Acute Intermittent Hypoxia | SHAM Acute Intermittent Hypoxia | Control Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 12 Participants | 13 Participants | 53 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 12 Participants | 13 Participants | 51 Participants |
| Sex: Female, Male Female | 16 Participants | 6 Participants | 8 Participants | 30 Participants |
| Sex: Female, Male Male | 12 Participants | 7 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 0 / 28 | 0 / 15 | 0 / 13 |
| serious Total, serious adverse events | 0 / 28 | 0 / 15 | 0 / 13 |
Outcome results
Primary
Change in Corticospinal Excitability
Transcranial magnetic stimulation (TMS) can be applied over the primary motor cortex to examine changes in corticospinal excitability. The downstream muscle activation can be recorded with surface EMG as a motor-evoked potential (MEP). The peak-to-peak MEP amplitude (mV) is as an index of corticospinal excitability. A randomized sequence of TMS intensities can be applied over the primary motor cortex, ranging from 90-140% of the participants' resting motor threshold (RMT). The mean MEP amplitude will be plotted against the corresponding stimulation intensity to produce the recruitment curve. The area under the recruitment curve is an additional index of corticospinal excitability (mV/% RMT).
Time frame: We will measure TMS before the start of 5 consecutive days of AIH or SHAM treatment. We will measure TMS within 24 hours of the final treatment.
Population: A total of 56 participants were enrolled for this study: Part 1: Motor Learning (N = 30; AIH group + control group) \& Part 2: Corticospinal Indices of Motor Learning (N = 36; AIH group + SHAM group). Changes in corticospinal excitability reflect the results from Part 2 of the study, which consisted of an AIH group and a SHAM group (i.e., blinded normoxia).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repetitive Acute Intermittent Hypoxia | Change in Corticospinal Excitability | 0.528 mV*percentage of RMT | Standard Error 0.188 |
| SHAM Acute Intermittent Hypoxia | Change in Corticospinal Excitability | 0.132 mV*percentage of RMT | Standard Error 0.188 |
p-value: 0.0098Mixed Models Analysis
Comparison: Linear regression analyses performed with the change in the MEP amplitude versus step length asymmetry.p-value: 0.014Regression, Linear
Comparison: Linear regression analyses performed with the change in the MEP amplitude versus step time asymmetry.p-value: 0.006Regression, Linear
Comparison: Linear regression analyses performed with the change in the MEP amplitude versus changes in net metabolic power.p-value: 0.001Regression, Linear
Primary
Net Metabolic Power
Using expired gas analyses, we will calculate net metabolic power by inputting steady-state values for V̇O₂ and V̇CO₂ into standard regression equations (W), subtracting resting values, and normalizing the result to each participant's body weight (kg).
Time frame: We will compare net metabolic power 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).
Population: A total of 56 participants were enrolled for this study: Part 1: Motor Learning (N = 30; AIH group + control group) \& Part 2: Corticospinal Indices of Motor Learning (N = 36; AIH group + SHAM group). Changes in net metabolic power reflect the results from Part 1 of the study, which consisted of an AIH group and a control group.~One participant was excluded from metabolic analysis due to RER \> 1.0, violating assumption that primarily oxidative pathways were being utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repetitive Acute Intermittent Hypoxia | Net Metabolic Power | 3.87 W/kg | Standard Deviation 0.397 |
| SHAM Acute Intermittent Hypoxia | Net Metabolic Power | 4.27 W/kg | Standard Deviation 0.766 |
p-value: 0.02ANOVA
Primary
Step Length Asymmetry
Step length asymmetry will be quantified as the ratio of the normalized difference in step lengths between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step length) / (Fast leg + Slow leg step length).
Time frame: We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).
Population: A total of 56 participants were enrolled for this study: Part 1: Motor Learning (N = 30; AIH group + control group) \& Part 2: Corticospinal Indices of Motor Learning (N = 36; AIH group + SHAM group). Changes in step length asymmetry reflect the results from Part 1 of the study, which consisted of an AIH group and a control group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repetitive Acute Intermittent Hypoxia | Step Length Asymmetry | -0.052 Ratio | Standard Deviation 0.023 |
| SHAM Acute Intermittent Hypoxia | Step Length Asymmetry | -0.0478 Ratio | Standard Deviation 0.024 |
p-value: 0.744ANOVA
Primary
Step Time Asymmetry
Step time asymmetry will be quantified as the ratio of the normalized difference in step times between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step time) / (Fast leg + Slow leg step time).
Time frame: We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).
Population: A total of 56 participants were enrolled for this study: Part 1: Motor Learning (N = 30; AIH group + control group) \& Part 2: Corticospinal Indices of Motor Learning (N = 36; AIH group + SHAM group). Changes in step time asymmetry reflect the results from Part 1 of the study, which consisted of an AIH group and a control group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Repetitive Acute Intermittent Hypoxia | Step Time Asymmetry | 0.0781 Ratio | Standard Deviation 0.021 |
| SHAM Acute Intermittent Hypoxia | Step Time Asymmetry | 0.0681 Ratio | Standard Deviation 0.0252 |
p-value: 0.269ANOVA