Measurement of Autonomic Cardiovascular Integrity in Persons With SCI

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by James J. Peters Veterans Affairs Medical Center
Sponsor:
Information provided by (Responsible Party):
Jill M. Wecht, Ed.D., James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT01758692
First received: December 27, 2012
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

People with a spinal cord injury (SCI) have limited ability to move and feel sensation below the level of the SCI. Doctors and researchers have tests which determine the level of function and sensation, this test was developed by the American Spinal Cord Injury Association (ASIA) and has been modified over the years to improve use and sensitivity. Most recently, the ASIA Injury classification Scale (AIS) was modified in 2011, but this test does not include the evaluation of autonomic nervous system (ANS) impairment. However, people with SCI do have impairment of the ANS and this may adversely affect how organ systems in the body function. Specifically, ANS impairment tends to result in changes in heart rate and blood pressure that may relate to the level of the SCI, but this is not fully understood. In this investigation we hope to develop simple tests which will allow doctors and scientist the ability to measure the amount of ANS impairment to the cardiovascular system, specifically the heart. The first part of the study will be to determine the heart rate response to several tests (administration of drugs and physical challenges) which will change heart rate. These tests will be given to people with and without SCI and the heart rate response will be compared between people with and without SCI. The bigger the difference in the heart rate response to these test between people with and without SCI the greater degree of ANS impairment in the people with SCI. Once this heart rate difference is determined, several simple tests (deep breathing, saliva test, Valsalva) will be performed in people with and without SCI to again compare the heart rate response. The second part of this study will be to determine if the heart rate responses to the first set of tests (administration of drugs and physical challenges) can predict the heart rate response to these simple tests (deep breathing, saliva test, Valsalva). The aim of this study is to develop a simple battery of tests which can be easily used by doctors and scientists to determine the degree of ANS impairment to the heart in persons with SCI.


Condition
Spinal Cord Injury

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Measurement of Autonomic Cardiovascular Integrity in Persons With SCI

Resource links provided by NLM:


Further study details as provided by James J. Peters Veterans Affairs Medical Center:

Primary Outcome Measures:
  • Autonomic Classification [ Time Frame: January 2015 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Edrophonium chloride as a test of cardio-vagal receptor integrity at the sinoatrial (SA) node [ Time Frame: January 2015 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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

Two catecholamine samples are collected either pre/post tilt (in the ICU) or positional shift (in the autonomics lab). Samples are collected once for individuals participants in the non-invasive testing only subgroup, twice for individuals participating in the ambulatory training subgroup, and on all 4 visits for individuals participating in the main group.


Estimated Enrollment: 100
Study Start Date: July 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Able-bodied Controls
10 controls between the ages of 18 and 65 of either gender; free of cardiovascular disease and/or medication.
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.

20 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.


  Eligibility

Ages Eligible for Study:   18 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Forty subjects with chronic SCI and 10 age and gender matched able-bodied controls will be recruited. A subgroup of 20 subjects with SCI will be recruited solely for the non-invasive portion of the study. These patients will not undergo the pharmacological/placebo administration or any of the manipulations being performed in the ICU. An additional 30 subjects will complete the non-invasive portion before and after completion of an ambulatory training protocol. This includes subjects who have completed various protocols in the Cardioautonomic Program or patients referred by their physician following routine physical examinations. Physicians will be informed of the inclusion and exclusion criteria for this study and will be able to provide us with the assurance that the patient is an appropriate candidate for the study and that he/she was willing to speak with the study coordinators.

Criteria

Inclusion Criteria:

For All Groups:

  • Age 18-65 years (18-89 years for Non-Invasive Only SCI Subjects)
  • Stable health for > 6 months
  • Non-smoker

    o Subjects with SCI:

  • Level of injury - C1-S4
  • Duration of injury - ≥ 1 year
  • AIS classification - A, B, C

Exclusion Criteria:

For Main Study SCI Group:

  • Tachycardia (resting HR ≥ 100 bpm)
  • Bradycardia (resting HR ≤ 40 bpm)
  • Hypertension
  • KNOWN:

Coronary artery disease, Chronic heart failure, Cardiac arrhythmias, Diabetes mellitus, Thyroid disease, Renal insufficiency, Hepatic disease, Autonomic neuropathy, Ulcerative colitis, Benign prostatic hyperplasia, Hiatal hernia, Glaucoma, Parkinson's disease, Stroke, other neuromuscular diseases, Known sulfite allergy or hypersensitivity, Asthma, Active illness or infection, For Non-invasives Only SCI Group

  • Diabetes mellitus
  • Autonomic neuropathy
  • Parkinson's disease
  • Active illness or infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01758692

Contacts
Contact: Dot M Fullwood, Masters of Science 7185849000 ext 1732 marvin.fullwood@va.gov
Contact: Jill M Wecht, Doctorate of Education 7185849000 ext 3122 jm.wecht@va.gov

Locations
United States, New York
James J Peters VA Medical Center Recruiting
Bronx, New York, United States, 10468
Contact: Jill M Wecht, Doctorate of Education    7185849000 ext 3122    jm.wecht@va.gov   
Contact: Dot M Fullwood, Masters of Science    7185849000 ext 1732    marvin.fullwood@va.gov   
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.         
Sponsors and Collaborators
James J. Peters Veterans Affairs Medical Center
Investigators
Principal Investigator: Jill M Wecht, Ed.D. JJPVAMC
  More Information

No publications provided

Responsible Party: Jill M. Wecht, Ed.D., Health Science Specialist, James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT01758692     History of Changes
Other Study ID Numbers: WEC-12-06, 01436
Study First Received: December 27, 2012
Last Updated: April 23, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Data and Safety Monitoring Board
United States: Food and Drug Administration

Keywords provided by James J. Peters Veterans Affairs Medical Center:
spinal cord injury
autonomic integrity
autonomic dysreflexia
baroreceptor integrity
sympathetic integrity
vagal integrity

Additional relevant MeSH terms:
Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on October 19, 2014