Sympathetic-Somatomotor Coupling in Human Spinal Cord Injury

Study Overview
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Brief Summary
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Significance: The long term objective of this study is to improve physical therapy and fitness programs in people with spinal cord injury. The results of the study will demonstrate the importance of matching blood flow to a muscle with exercise of that same muscle. Scientific Objective: The objective of the study is to measure how the body regulates bloodflow to a muscle during exercise. We intend to study these effects by triggering blood flow changes during movement, and measuring bloodflow changes during exercise in people with spinal cord injury. We will also look at the long term effects of different exercise programs on bloodflow during exercise. Study Populations: This study will involve people with partial spinal cord injury and age and sex matched controls without injury. Specific Aims: Aim 1 will be to measure bloodflow during exercise of the legs (below the injury). This aim will examine the control of bloodflow and muscle contractions and how it changes after spinal cord injury. Aim 2 will then look at changes in bloodflow during exercise after training. Three different eight week exercise training programs will be tested including 1) upper body ergometry, 2) treadmill training with exertion level matched to the upper body ergometry and 3) treadmill training with heart rate matched to an initial test of upper body ergometry.

Detailed Description
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The regulation of cardiovascular systems during muscle activity is poorly understood in people with incomplete spinal cord injury (SCI). In the past, disruptions in somatomotor and sympathetic control have been investigated separately in SCI. We propose to investigate the coupling of sympathetic and somatomotor control because it is relevant to exercise training paradigms that are designed to improve somatomotor function or enhance physical fitness. Our approach will be to measure tendon tap reflexes, voluntary muscle activation, and blood flow of the knee (below injury) and elbow (above injury) before and after sympathetic stimuli consisting of cold pressor tests, mental math and an acute bout of exercise. These data will provide information about sympathetic control of blood flow during muscle activity. Plasticity of the sympatheticsomatomotor coupling will also be investigated by making measurements before and after a treadmill training exercise program. These experiments will enable us to address three aims. Aim 1 will be to characterize coupling of sympathetic and somatomotor systems below the level of spinal injury. This aim will examine spinal sympathetic and motor reflexes and their interactions. It will also examine how descending somatomotor coupling is disrupted by the spinal injury. In Aim 2, we will identify changes in the interactions of sympathetic and somatomotor systems above a spinal injury. Because of the injury and the changes that occur below the injury, the sympathetic-somatomotor coupling is also likely to be disrupted in the arm. Aim 3 will then demonstrate plasticity of sympathetic-somatomotor coupling after exercise training. Three different eight week exercise training programs will be tested including 1) treadmill training with exertion level matched to 70-80% of HRR 2)treadmill training with 30-40% HRR. The exercise training will be tested in a randomized crossover study design with one month between exercise training paradigms. We anticipate that there will be plasticity of sympathetic-somatomotor coupling and that the exercise training effects will normalize control of these systems. However, because of the injury, we anticipate that adaptations will differ from non-injured controls. This study has implications for exercise training in human SCI. The coupling of sympathetic and somatomotor systems is expected to depend on whether exercise targets the upper or lower body. The recovery of function requires both the improvement in the control of movement as well as in the regulation of blood flow to active muscle groups. In addition, this study is important for understanding the potential impact of treadmill exercise training on cardiovascular fitness, a topic of increasing interest in people with limitations to physical activity.

Official Title
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Sympathetic-Somatomotor Coupling in Human Spinal Cord Injury

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Other: Treadmill Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: incomplete SCI subjects will be over age 18 to fit in the apparatus and to assure a mature gait pattern at least 6 months post injury, and medically stable with an incomplete lesion between levels T1-T10 lower extremity motor score of 10 or greater presence of intact stretch reflexes, detected clinically no previous history or evidence of peripheral nerve damage in the lower extremities Subjects must be able to step on a treadmill with no more than 40% body weight support. Healthy controls will be age and sex matched to the subjects with spinal cord injury. Exclusion Criteria: unhealed decubiti, bladder or other infection severe contracture or osteoporosis heterotopic ossification cardiac arrhythmia inability to give informed consent an episode of autonomic dysreflexia in the past year use of spasticity or cardiovascular medications (e.g. baclofen)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: One day testing<br>Aim 1 will be to measure bloodflow during exercise of the legs (below the injury). This aim will examine the control of bloodflow and muscle contractions and how it changes after spinal cord injury. | |
| Experimental: Effects of long term training<br>Aim 3 will then look at changes in bloodflow during exercise after training. Three different eight week exercise training programs will be tested including 1) treadmill training at high intensity as defined by 70-80% of HRR or 15-17 RPE 2) treadmill training at low intensity as defined by 30-40% of HRR or <13 RPE | Other: Treadmill Training<br>* Subjects will be randomized to a high intensity and low intensity group. The high intensity group will train at 70-80% of their HRR and the low intensity group will train at 30-40% of their HRR.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial blood flow | Subject will be tested with doppler ultrasonography immediately pre and post sympathetic stressor. Testing sessions will take anywhere between 3-6 hours. | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graded Treadmill Exercise Test | Graded treadmill exercise test will be tested at multiple intervals pre and post training paradigms. | 15 months | 
| Heart rate | Heart rate will be tested continuously during sympathetic stressors and at multiple intervals pre and post training paradigms with a Finapres. | 15 months | 
| Knee torque | Knee torque will be tested with the Biodex both pre and post sympathetic stressors. | 8 hours | 
| Tendon tap reflexes | Tendon tap reflexes will be tested during one day testing pre and post sympathetic stressors. | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injury, sympathetic nervous system, locomotor training, exercise