Spinal Cord InjuryNCT01758692
Measurement of Autonomic Cardiovascular Integrity in Persons With SCI
An observational study of Spinal Cord Injury, run by James J. Peters Veterans Affairs Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injury
- How many people
- 177 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to 30 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Diabetes mellitus
- Autonomic neuropathy
- Parkinson's disease
- Active illness or infection
Trial locations and contacts
1 site in 1 country.
United States1 site
James J Peters VA Medical Center
The Bronx, New York, 10468
About this study
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.
- Conditions
- Spinal Cord Injury
- Keywords
- spinal cord injury, autonomic integrity, autonomic dysreflexia, baroreceptor integrity, sympathetic integrity, vagal integrity
- Medical subject headings
- Spinal Cord Injuries, Autonomic Dysreflexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Able-bodied Controls | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autonomic Classification
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.
Measured: January 2015
Secondary outcomes (5)
Edrophonium chloride as a test of cardio-vagal receptor integrity at the sinoatrial (SA) node
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.
Measured: January 2015
Glycopyrrolate as a test of cardio-vagal efferent integrity
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.
Measured: January 2015
Esmolol hydrochloride as a test of cardiac-specific (β1) sympathetic receptor integrity
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).
Measured: January 2015
Cold Face Test
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.
Measured: January 2015
Head-up Tilt Test
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.
Measured: January 2015
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2013 (estimated)
- Study startJul 2012
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- James J. Peters Veterans Affairs Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Jill M. Wecht, Ed.D., James J. Peters Veterans Affairs Medical Center
- Investigators
- Jill M Wecht, Ed.D., Principal investigator, JJPVAMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01758692
- Sponsor's protocol ID
- WEC-12-06
- Other IDs
- 01436
- Status last verified
- Jun 2023
- First submitted
- 27 Dec 2012
- Last updated
- 26 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Wecht JM, Maher MT, Kirshblum SC, Escalon MX, Weir JP. Sit-up test to assess orthostatic hypotension in individuals with spinal cord injury. Clin Auton Res. 2025 Jun;35(3):393-405. doi: 10.1007/s10286-024-01102-8. Epub 2025 Mar 4.
PubMed 40032720
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Autonomic Cardiovascular Integrity in Persons With SCI
- ClinicalTrials.gov ID
- NCT01758692
- Acronym / sponsor ID
- WEC-12-06
- Conditions
- Spinal Cord Injury
- Keywords
- spinal cord injury, autonomic integrity, autonomic dysreflexia, baroreceptor integrity, sympathetic integrity, vagal integrity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- James J. Peters Veterans Affairs Medical CenterUS federal agency
- Study start
- Jul 2012 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 1 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Able-bodied Controls | – | –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. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- Age 18-65 years (18-89 years for Non-Invasive Only SCI Subjects)
- Stable health for > 6 months
- Non-smoker
- Level of injury - C1-S4
- Duration of injury - ≥ 1 year
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
Edrophonium chloride as a test of cardio-vagal receptor integrity at the sinoatrial (SA) node
Time frame: January 2015
Glycopyrrolate as a test of cardio-vagal efferent integrity
Time frame: January 2015
Esmolol hydrochloride as a test of cardiac-specific (β1) sympathetic receptor integrity
Time frame: January 2015
Cold Face Test
Time frame: January 2015
Head-up Tilt Test
Time frame: January 2015
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2023.
- Derived from this study: PubMed 40032720Wecht JM, Maher MT, Kirshblum SC, Escalon MX, Weir JP. Sit-up test to assess orthostatic hypotension in individuals with spinal cord injury. Clin Auton Res. 2025 Jun;35(3):393-405. doi: 10.1007/s10286-024-01102-8. Epub 2025 Mar 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jill M Wecht, Ed.D. principal investigator
JJPVAMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Cord Injury, run by James J. Peters Veterans Affairs Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autonomic Classification (time frame: January 2015). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01758692, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2023.