Measurement of Autonomic Cardiovascular Integrity in Persons With SCI
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|ClinicalTrials.gov Identifier: NCT01758692|
Recruitment Status : Recruiting
First Posted : January 1, 2013
Last Update Posted : February 1, 2018
|Condition or disease|
|Spinal Cord Injury|
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Measurement of Autonomic Cardiovascular Integrity in Persons With SCI|
|Study Start Date :||July 2012|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
10 controls between the ages of 18 and 65 of either gender; free of cardiovascular disease and/or medication.
An addition 40 controls ages 18-89 of either gender, will perform the non-invasive manipulations only.
Spinal Cord Injury
40 subjects to perform the pharmacological and non-invasive manipulations; between the ages of 18 and 65 years old in stable health for the last 6 months, non-smoker, and level of injury from C1 - S4 for over 1 year and an AIS classification of A, B, C. Free of arrhythmia, hypertension, cardiovascular disease, kidney disease, diabetes, neuropathies, neuromuscular disease, and sulfite allergies or hypersensitivity.
60 subjects to perform the non-invasive manipulations only; between 18-89 years of age in stable condition (>6 months), non-smoker. Level of injury from C1-S4 for over a year with a AIS classification of A, B, or C. No history of diabetes, autonomic neuropathy, parkinson's disease, or acute illness or infection. An additional 30 will perform the non-invasive testing before and after completion of an ambulatory training protocol.
- Autonomic Classification [ Time Frame: January 2015 ]To characterize the individual level and completeness of autonomic impairment using simultaneous pharmacological and physical provocation in persons with SCI with varying AIS classifications of motor/sensory impairment. From these studies we anticipate a more precise diagnosis of the degree of autonomic cardiovascular impairment in individuals with SCI. Data from the pharmacologic and physical interventions will be used to determine the validity of currently available clinical tools used in other populations of autonomic failure to diagnose the degree of cardiovascular autonomic impairment for use in the SCI population.
- Edrophonium chloride as a test of cardio-vagal receptor integrity at the sinoatrial (SA) node [ Time Frame: January 2015 ]The heart rate (HR) response to exogenous cholinergic stimulation with edrophonium will be compared at rest and during the CFT between the non-SCI and SCI. We expect the resting HR response to edrophonium will be comparable in individuals with SCI and non-SCI controls, suggesting integral SA-node receptor responsiveness to acetylcholine (vagal) stimulation.
- Glycopyrrolate as a test of cardio-vagal efferent integrity [ Time Frame: January 2015 ]The HR response to the CFT (bradycardia) will be compared with and without glycopyrrolate in the SCI and non-SCI subjects. We expect the HR response to the CFT (endogenous stimulation of cardio-vagal efferent activation), which induces bradycardia, will be blunted following glycopyrrolate administration in the non-SCI control subjects, but the HR response to the CFT will be unaffected by glycopyrrolate in the SCI subjects.
- Esmolol hydrochloride as a test of cardiac-specific (β1) sympathetic receptor integrity [ Time Frame: January 2015 ]To compare the HR response to β1 receptor blockade in the resting and head-up tilt (HUT) states between individuals with SCI and non-SCI controls. We expect the resting HR will be lower and the HR response to HUT will be blunted following administration of Esmolol in the non-SCI controls; these HR responses will be attenuated in persons with SCI, and the degree of blunting will be categorically delineated by level of lesion (i.e., above T1, T2-T6, T7 and below).
- Cold Face Test [ Time Frame: January 2015 ]For the CFT, the data will be analyzed using a three-factor mixed ANOVA. The dependent variable will be 20 second average heart rate. The ANOVA will incorporate two between-subjects factors: 1) groups (levels = control, low paraplegia, high paraplegia, and tetraplegia), and 2) drug (levels = placebo, edrophonium, glycopyrrolate, glycopyrrolate & esmolol). The within subjects factor is time (levels = pre-CFT and post-CFT). From our previous pilot studies examining differences in HR response to CFT between control subjects and subjects grouped by SCI level, we found mean differences between groups > 11 beats per minute with a pooled standard deviation of ~ 8.5 beats per minute. Using these estimates, with 10 subjects per group we will have over 99% power to detect differences between groups at an alpha level of 0.05. Using a 50% more conservative effect size estimate, with 10 subjects per group we will have ~ 85% power to detect differences between groups at an alpha level of 0.05.
- Head-up Tilt Test [ Time Frame: January 2015 ]For the HUT, the data will be analyzed using a three-factor mixed ANOVA. The dependent variable will be 20 second average heart rate. The ANOVA will incorporate two between-subjects factors: 1) groups (levels = control, low paraplegia, high paraplegia, and tetraplegia), and 2) drug (levels = placebo, edrophonium, glycopyrrolate, and glycopyrrolate + esmolol). The within subjects factor is time (levels = pre-HUT and post-HUT). From our previous pilot studies examining differences in HR response to HUT between control subjects and subjects grouped by SCI level, we found mean differences between groups > 3 beats per minute with a pooled standard deviation of ~ 5 beats per minute. Using these estimates, with 10 subjects per group we will have 85% power to detect differences between groups at an alpha level of 0.05.
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01758692
|Contact: Matthew T Maher, MS||7185849000 ext email@example.com|
|Contact: Jill M Wecht, Ed.D||7185849000 ext firstname.lastname@example.org|
|United States, New York|
|James J Peters VA Medical Center||Recruiting|
|Bronx, New York, United States, 10468|
|Contact: Jill M Wecht, Ed.D 718-584-9000 ext 3122 email@example.com|
|Contact: Matthew T Maher, MS 7185849000 ext 1706 firstname.lastname@example.org|
|Principal Investigator: Jill M Wecht, Ed.D.|
|Sub-Investigator: Gregory Schilero, M.D.|
|Sub-Investigator: Miroslav Radulovic, M.D.|
|Sub-Investigator: William A Bauman, M.D.|
|Principal Investigator:||Jill M Wecht, Ed.D.||JJPVAMC|