Clinical trial NCT02396823: Respiratory Motor Control and Blood Pressure Regulation After Spinal Cord Injury
Official title: Respiratory Motor Control and Blood Pressure Regulation After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injury
Keywords: Blood pressure regulation
Respiratory Muscle Training
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-03-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The proposed study is designed to answer a novel research question: Can resistive respiratory muscle training designed to improve respiratory motor control also improve blood pressure regulation impaired by spinal cord injury? Resistive breathing exercise, or respiratory muscle training, has been applied to rehabilitate breathing after spinal cord injury, but has not been evaluated as a method for increasing resting blood pressure and / or improving its regulation under stress as is planned in the proposed project. For the first time, respiratory muscle training intervention will be used as a tool to investigate the physiological relationships between pulmonary and cardiovascular function in individuals with Spinal Cord Injury (SCI). Thus, it will foster a new direction from which to address neglected issues surrounding the cardiovascular complications of spinal cord injury.

Detailed description: Screening:

To aid in determining eligibility, participants will have a respiratory and cardiovascular function tests. The participants will also have an ASIA (American Spinal Injury Association) exam to grade the degree and level of their SCI.

Enrollment:

Following screening process, consenting and recruiting, the experimental recordings:

1. Pulmonary Function Test- This test measures lung volumes, airflow and airway pressure with standard equipment;
2. Respiratory Motor Control Assessment- Pulmonary function test is repeated while participant is sitting in a special hospital bed and lying on their back while the investigators record electrical impulses from their neck, chest, arms, legs, abdomen and back muscles. These impulses record how their muscles are contracting. The investigators also record how their chest and abdomen are moving by placing elastic belts around their chest and abdomen. Blood pressure will be measured using a finger cuff;
3. Orthostatic stress test- Using the same methods as above, the investigators will measure blood pressure, heart rate and chest and abdomen movements while the participant is lying down on their back and when the position is suddenly changed to sitting in the investigators' cardiac chair or to upright vertical position on a Tilt table. The investigators will measure blood samples at several intervals from a small catheter inserted into the vein in the arm.
4. Ultrasound of the heart will be performed before and after the Respiratory Muscle Training (RMT) program.

RMT:

During the training session, subjects will be seated in their personal wheelchair with an approximately 45° head-up tilt with nose clip on. Standard threshold Positive Expiratory Pressure Device or standard threshold Inspiratory Muscle Trainer or combination of both will be used to breathe through with adjustable resistance ranging of 20 to 41 cm of water.

All of these devices are in routine clinical use. These devices will be assembled together using a T-shaped connector with flanged mouthpiece. The participants will be instructed to perform inspiratory and expiratory efforts against a resistive load. During inhalation, the subjects will be instructed to sustain the effort until their lungs feel full. During exhalation, the subjects will be instructed to sustain their effort until their lungs feel empty.

This study will use two test-subject pre-training assessment sessions to provide its internal experimental group control. To match the training period (4 weeks), the pre-training assessment sessions will be performed four weeks apart and the measured parameters will be used to establish the variance in untrained subjects. The pulmonary function tests include the measurement of lung volume, airflow, and static mouth airway pressures using standard clinical methods and equipment while the SCI participant is sitting in their personal wheelchair. The investigators will also record the surface electromyogram (sEMG) activity from the trunk muscles during Maximal Inspiratory Pressure (PImax) and Maximal expiratory pressure (PEmax) measurements in supine position (PImax and PEmax tasks). The investigators will measure a Sympathetic Skin Response (SSR) by recording limb skin resistance during neural stimulations. The investigators will assess beat-to-beat systemic blood pressure, heart rate and cardiac output will be recorded during the orthostatic stress test. In addition, during the orthostatic stress test, the investigators will collect venous blood samples to measure the levels of catecholamines. In addition to the beat-to beat calculated, resting cardiac output will be measured by ultrasonic cardiac echography. After these initial tests, participants will be assigned to RMT. The participants in experimental group will complete the study after 4 weeks of training totaling 20 sessions of 45 minutes per day carried out 5 days per week. The testing battery will be repeated immediately after completing the training and repeatedly during the follow-up period. Ten matched control subjects will undergo the same procedures except training.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years old;
2. stable medical condition without diseases or autonomic dysreflexia that would contraindicate RMT;
3. no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore or urinary tract infection that might interfere with RMT;
4. no clinically significant depression, psychiatric disorders or ongoing drug abuse;
5. clear indications that the period of spinal shock is concluded determined by presence of muscle tone, deep tendon reflexes or muscle spasms;
6. no current anti-spasticity medication regimen;
7. non-progressive C3-T5 American Spinal Cord Injury Association Designation of A-D SCI;
8. not ventilator dependent for respiration;
9. sustained SCI at least 6 months prior to entering the study;
10. at least 15%-deficit in pulmonary function outcomes (FVC and FEV1) detected by screening spirometry; and
11. orthostatic hypotension (the decrease 20mm Hg or more in systolic or a reduction 10mm Hg or more in diastolic blood pressure on changing body position from a supine to an upright) detected by screening orthostatic stress test

Exclusion Criteria:

1. a presence of major cardiovascular or pulmonary disease, endocrine disorders, malignancy, marked obesity, deep vein thrombosis, and major gastrointestinal problem such as swallowing or other major medical illness contraindicated for respiratory muscle training or testing.
2. Pregnant women are excluded from this study, as the risk to the fetus is unknown. No pregnancy test or birth control regimen will be required.

Primary outcomes:
measure: Changes in Pulmonary Function Test outcomes
timeFrame: At baseline, after 1-month long respiratory training, and during 6 months of follow-up period
Secondary outcomes:
measure: Changes in Respiratory Motor Control Assessment outcomes
timeFrame: At baseline, after 1-month long respiratory training, and during 6 months of follow-up period
measure: Changes in Orthostatic Stress Test outcomes
timeFrame: At baseline, after 1-month long respiratory training, and during 6 months of follow-up period
measure: Changes in cardiac output
timeFrame: At baseline, after 1-month long respiratory training, and during 6 months of follow-up period
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Frazier Rehabilitation and Neuroscience Institute
state: Kentucky
Study officials:
affiliation: avovec02@louisville.edu
name: Alexander Ovechkin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Legg Ditterline BE, Aslan SC, Randall DC, Harkema SJ, Castillo C, Ovechkin AV. Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury. Arch Phys Med Rehabil. 2018 Mar;99(3):423-432. doi: 10.1016/j.apmr.2017.06.033. Epub 2017 Aug 9.