Spinal Cord Injuries, Brown Sequard, Central Cord Syndrome
Conditions
Keywords
Respiration, Spinal cord injuries, Walking recovery
Brief summary
Change to Reflect What Was Done and reason Changes Were Made. The purpose of this study is to determine (1) if a specific breathing treatment (intermittent hypoxia) can promote changes in breathing function and (2) if pairing breathing treatments (hypoxia) with locomotor training can enhance the benefits of walking recovery observed with locomotor training alone (without breathing treatments).
Detailed description
Spinal cord injury (SCI) is a very disabling health problem. Paralysis and paresis of limb and trunk muscles are major consequences of SCI and result in the inability to walk or difficulty walking. The most commonly stated goal by individuals with SCI during rehabilitation is the desire to walk again. Locomotor training (LT) that uses a body-weight support system and treadmill (BWST) is a task-specific rehabilitation intervention that allows practice of walking at normal speeds while loading the lower extremities, facilitating upright posture, and hip extension. Substantial improvement in ambulation can occur following locomotor training (LT) in individuals with motor incomplete spinal cord injury (iSCI). Despite these advances in activity-dependent rehabilitation, a need exists for defining complementary strategies that further amplify endogenous neuroplasticity. The proposed study will assess the therapeutic potential of (1) a respiratory training intervention (acute intermittent hypoxia, or AIH) on breathing function and (2) a combined locomotor (LT) and respiratory (AIH) training intervention for enhancing walking recovery.
Interventions
OTHERIntermittent Hypoxia
Individuals received exposure to intermittent hypoxia for 10 days, and placebo for 1-2 days.
OTHERLocomotor Training
Individuals received 10 days of locomotor training, intense walking training on a treadmill with body weight support. Manual assistance was provided at the legs to optimize stepping patterns.
Sponsors
University of Florida
Wayne State University
VA Office of Research and Development
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults at least 18 years of age * At least 12 months post-incomplete spinal cord injury (I-SCI), including but not limited to the following syndromes: Brown Sequard and Central Cord Syndromes * Upper motor neuron lesion (with upper motor neuron signs (i.e. presence of clonus, spasms, and/or hyperreflexia)) * A diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic pathology * Resting oxygen saturation (SpO2) levels of 95-99% * Individuals who ambulate independently, with an assistive device, or who can walk when provided manual assistance * Persons using anti-spasticity medication must maintain stable medication dosage during the study * Able to give informed consent. * Medical approval by individual's physician
Exclusion criteria
* Current participation in a rehabilitation program/research protocol that could interfere or influence the outcome measures of the current study * History of congenital SCI (e.g. myelomeningocele, intraspinal neoplasm, Frederich's ataxia) or other degenerative spinal disorders (e.g. spinocerebellar degeneration, syringomyelia) that may complicate the protocol * Inappropriate or unsafe fit of the harness due to the participant's body size and/or joint contractures or severe spasticity that would prohibit the safe provision of either training modality. * Severe spasticity that would prohibit the safe provision of training. * Pregnancy - all women of childbearing age will be required to undergo pregnancy testing prior to enrollment * Unstable medical condition that could interfere with safety during participation in study (i.e. symptomatic cardiopulmonary complication, osteoporosis, contractures or other significant medical complications that would prohibit or interfere with testing of walking function and training or alter compliance with a training protocol)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minute Ventilation - Phase 2 | Pre- versus Post-treatment | Minute ventilation (Ve) is the volume of gas inhaled or exhaled from a person's lungs per minute. Minute ventilation during the end-recovery (ER) period at initial (i.e., Days 1 and 2, initial ER period) and final (i.e., Days 9 and 10, final ER period) days of the IH protocol were normalized to values from baseline with elevated carbon dioxide (B2) within each individual session to characterize daily effects of exposure to IH at the beginning and end of treatment. Values from baseline with elevated carbon dioxide and the ER period during the final days of the protocol (final B2 and final ER period, respectively) also were normalized to elevated carbon dioxide baseline during initial days of the protocol (initial B2) to describe the cumulative effects of repeated exposure to IH. Outcomes are reported as % increases in minute ventilation during initial and final treatment sessions for daily/acute effects and cumulative/chronic effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilatory Loading - Phase 3 | Pre- versus Post-treatment | Ventilatory load compensation was assessed in two ways. Mean slopes for (1) pressure vs. resistance (P vs R) and (2) airflow vs. resistance (AF vs R) were calculated for pre- and post-IH treatment. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from October, 2010 through April, 2014 through the North Florida/South Georgia VA Medical Center's Brain Rehabilitation Research Center.
Pre-assignment details
Different study arms were carried out in different phases. The time individuals were enrolled determined which arm they were involved with. Participants enrolling knew which arm we currently were recruiting for. Individuals enrolled in early arms were invited back to other arms of the study if they chose--however, this was not a requirement.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Arm (Pilot) This group of participants were exposed to intermittent hypoxia and/or locomotor training. They were enrolled only to establish and streamline the protocol and train the laboratory personnel. | 3 |
| Phase 2 Arm (Long Term Facilitation) This group of subjects were exposed to intermittent hypoxia and minute ventilation was recorded to determine whether ventilatory long term facilitation (LTF) was present. | 8 |
| Phase 3 Arm (Ventilatory Loading) This group of subjects was exposed to intermittent hypoxia and ventilatory loading was assessed. | 3 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal By Subject or Failed Screen | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Phase 1 Arm (Pilot) | Phase 2 Arm (Long Term Facilitation) | Phase 3 Arm (Ventilatory Loading) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 2 Participants | 11 Participants |
| Age, Continuous | 52 years | 53.13 years | 48.33 years | 51.86 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 3 Participants | 14 Participants |
| Region of Enrollment United States | 3 participants | 8 participants | 3 participants | 14 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 10 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 10 | 0 / 3 |
Outcome results
Primary
Minute Ventilation - Phase 2
Minute ventilation (Ve) is the volume of gas inhaled or exhaled from a person's lungs per minute. Minute ventilation during the end-recovery (ER) period at initial (i.e., Days 1 and 2, initial ER period) and final (i.e., Days 9 and 10, final ER period) days of the IH protocol were normalized to values from baseline with elevated carbon dioxide (B2) within each individual session to characterize daily effects of exposure to IH at the beginning and end of treatment. Values from baseline with elevated carbon dioxide and the ER period during the final days of the protocol (final B2 and final ER period, respectively) also were normalized to elevated carbon dioxide baseline during initial days of the protocol (initial B2) to describe the cumulative effects of repeated exposure to IH. Outcomes are reported as % increases in minute ventilation during initial and final treatment sessions for daily/acute effects and cumulative/chronic effects.
Time frame: Pre- versus Post-treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2 Arm (LTF) | Minute Ventilation - Phase 2 | Daily Acute Effects - Initial | 22.0 percentage of baseline | Standard Error 5.2 |
| Phase 2 Arm (LTF) | Minute Ventilation - Phase 2 | Daily Acute Effects - Final | 18.6 percentage of baseline | Standard Error 3.6 |
| Phase 2 Arm (LTF) | Minute Ventilation - Phase 2 | Cumulative Effects - Initial | 22.0 percentage of baseline | Standard Error 5.2 |
| Phase 2 Arm (LTF) | Minute Ventilation - Phase 2 | Cumulative Effects - Final | 22.1 percentage of baseline | Standard Error 6.9 |
Comparison: Daily acute and cumulative Pre vs Post comparisonsp-value: <0.001Two-way RMANOVA Student-Newman-Keuls
Secondary
Ventilatory Loading - Phase 3
Ventilatory load compensation was assessed in two ways. Mean slopes for (1) pressure vs. resistance (P vs R) and (2) airflow vs. resistance (AF vs R) were calculated for pre- and post-IH treatment.
Time frame: Pre- versus Post-treatment
Population: Data were collected from 3 participants. However, clinical observations revealed results of interest from only 1/3 of the participants. Therefore, data from only this 1 individual were analyzed for presentation as a case study. The data from the other 2 participants were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 3 Arm (Ventilatory Loading) | Ventilatory Loading - Phase 3 | P vs R Baseline | -0.12 unitless | Standard Error 0.02 |
| Phase 3 Arm (Ventilatory Loading) | Ventilatory Loading - Phase 3 | P vs R Post Day 10 IH | -0.17 unitless | Standard Error 0.02 |
| Phase 3 Arm (Ventilatory Loading) | Ventilatory Loading - Phase 3 | AF vs R Baseline | -0.003 unitless | Standard Error 0.001 |
| Phase 3 Arm (Ventilatory Loading) | Ventilatory Loading - Phase 3 | AF vs R Post Day 10 IH | -0.0004 unitless | Standard Error 0.002 |
Comparison: Compared outcomes from Baseline versus Post-Day 10 IH for mean slope of AF vs. Resistancep-value: <0.05RMANOVA and Student-Neuman-Keuls
Comparison: Compared outcomes from Baseline versus Post-Day 10 IH for mean slope of of Pressure vs. Resistancep-value: <0.05RMANOVA and Student-Neuman-Keuls