Autonomic Function Testing for Spinal Cord Injury

Recruiting at 1 trial location

Overseen By PI

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Blood thinners

Disqualifiers: Cardiovascular disease, Hypertension, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

69 Participants Needed

Trial Summary

What is the purpose of this trial?

This study looks to characterize gradients of dysfunction in the autonomic nervous system after spinal cord injury. The autonomic nervous system plays key roles in regulation of blood pressure, skin blood flow, and bladder health- all issues that individuals with spinal cord injury typically suffer. Focusing on blood pressure regulation, the most precise metric with broad clinical applicability, the investigators will perform laboratory-based tests to probe the body's ability to generate autonomic responses. For both individuals with spinal cord injury and uninjured controls, laboratory-based experiments will utilize multiple parallel recordings to identify how the autonomic nervous system is able to inhibit and activate signals. The investigators anticipate that those with autonomic dysfunction after spinal cord injury will exhibit abnormalities in these precise metrics. The investigators will further have research participants wear a smart watch that tracks skin electrical conductance, heart rate, and skin temperature, which can all provide clues as to the degree of autonomic dysfunction someone may suffer at home. The investigators will look to see if any substantial connections exist between different degrees of preserved autonomic function and secondary autonomic complications from spinal cord injury. In accomplishing this, the investigators hope to give scientists important insights to how the autonomic nervous system works after spinal cord injury and give physicians better tools to manage these secondary autonomic complications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking blood thinners.

What data supports the effectiveness of this treatment for autonomic dysreflexia in spinal cord injury?

The research highlights that sympathetic skin responses (SSRs) are useful in assessing autonomic dysfunction in spinal cord injury, which includes autonomic dysreflexia. SSRs are a quick and non-invasive way to evaluate the severity of autonomic issues, suggesting they could help in understanding and managing autonomic dysreflexia. ^{1 2 3 4 5}

Is autonomic function testing for spinal cord injury safe?

Autonomic function testing, such as urodynamic studies, can trigger autonomic dysreflexia (a sudden increase in blood pressure) in people with spinal cord injuries, especially those with injuries above the T6 level. While no long-term complications were reported in one incident, the potential for severe cardiovascular issues means careful monitoring is important during these tests. ^{1 6 7 8 9}

How does this treatment for spinal cord injury differ from other treatments?

This treatment is unique because it focuses on autonomic function testing, which is a non-invasive method to assess the autonomic nervous system's role in spinal cord injury. Unlike other treatments that may focus on sensorimotor recovery, this approach uses sympathetic skin responses to evaluate autonomic dysfunction, providing insights into conditions like autonomic dysreflexia and orthostatic hypotension. ^{1 3 5 6 10}

Research Team

Ryan Solinsky, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults aged 18-50 with adult onset, traumatic spinal cord injury that occurred 1-5 years ago. They should have a range of autonomic dysfunction (American Spinal Injury Association Impairment Scale A-D) and injuries at the C1-T12 level. Exclusions include blood thinners use, incompatible implants with MRI, pregnancy, lactation, cognitive issues preventing consent, BMI >30 kg/m2 for controls only.

Inclusion Criteria

If you have a spinal cord injury, it must be classified as A-D on the American Spinal Injury Association Impairment Scale, which measures the severity of your injury.

If you have a spinal cord injury, it must be at a certain level defined by specific guidelines.

My spinal cord injury was caused by trauma as an adult.

Exclusion Criteria

I am not pregnant or breastfeeding.

I am able to understand and give consent for my participation.

I am currently on blood thinners.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including the Autonomic Dysfunction Following Spinal Cord Injury questionnaire and the Composite Autonomic Symptom Score

1 week

1 visit (in-person)

Laboratory Diagnostic Testing

Participants undergo laboratory-based tests to assess autonomic nervous system function, including Valsalva maneuver, ECG, blood pressure monitoring, and smartwatch assessments

1 week

1 visit (in-person)

Follow-up

Participants are monitored for any changes in autonomic function and secondary complications

4 weeks

Treatment Details

Interventions

• Testing of autonomic dysreflexia
• Tests of sympathetic activation
• Tests of sympathetic inhibition

Trial Overview The study tests how well the autonomic nervous system functions after spinal cord injury by measuring blood pressure regulation and other responses. It includes lab tests to assess signal inhibition/activation in participants with injuries versus uninjured controls, smart watch monitoring at home for heart rate and skin temperature data, and MRI scans to analyze spinal cord connectivity patterns.

Participant Groups

Group I: Individuals without spinal cord injury Experimental Treatment 3 Interventions

Group II: Individuals with spinal cord injury Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Recruited

11,200+

Findings from Research

In a study of 78 male patients with spinal cord injury experiencing autonomic dysreflexia (AD), it was found that AD episodes were predominantly associated with relative tachycardia (68.0%), indicating a common cardiovascular response during these episodes.

The use of nitroglycerin ointment for bladder-related AD episodes resulted in a quicker reduction in blood pressure compared to non-bladder related episodes, suggesting it may be an effective treatment option for managing AD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring detailed characteristics of autonomic dysreflexia. Solinsky, R., Kirshblum, SC., Burns, SP.[2023]

A study involving 120 physiotherapists (52 undergraduates and 68 postgraduates) revealed that knowledge about autonomic dysreflexia (AD) was generally low, with 96.2% of undergraduates and 86.8% of postgraduates rating their knowledge as poor or nonexistent.

Higher knowledge scores were linked to having a master's degree, more than 5 years of practice, and more frequent interactions with patients who have spinal cord injuries, indicating a need for improved education on AD in physiotherapy training programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What do physiotherapists and physiotherapy students know about autonomic dysreflexia? Tederko, P., Ugniewski, K., Bobecka-Wesołowska, K., et al.[2021]

A 73-year-old male with cervical stenosis experienced autonomic dysreflexia (AD) symptoms, including hot flashes and palpitations, which were resolved after undergoing anterior cervical decompression and fusion surgery.

This case suggests that autonomic dysreflexia can occur due to cervical spinal stenosis, highlighting the need for clinicians to consider this association beyond typical spinal cord injury cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia caused by cervical stenosis. Khanna, K., Theologis, AA., Tay, B.[2022]

In a study of 10 subjects with complete spinal cord injury above T6, silent autonomic dysreflexia was frequently observed during routine bowel programs, with significant increases in systolic blood pressure (SBP) noted.

Despite no subjects reporting classic symptoms of autonomic dysreflexia, 60% experienced SBP increases above 150 mmHg, indicating a need for further research on potential preventative measures or treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Silent autonomic dysreflexia during a routine bowel program in persons with traumatic spinal cord injury: a preliminary study. Kirshblum, SC., House, JG., O'connor, KC.[2022]

Sympathetic skin responses (SSRs) are a quick and non-invasive way to assess autonomic dysfunction in patients with spinal cord injury (SCI), showing that autonomic impairment can occur independently of sensorimotor issues.

The review emphasizes the importance of using SSRs alongside other validated tests to better predict and document autonomic dysfunction, particularly conditions like autonomic dysreflexia and orthostatic hypotension in SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sympathetic skin responses and autonomic dysfunction in spinal cord injury. Berger, MJ., Hubli, M., Krassioukov, AV.[2014]

In a study of 48 spinal cord injury patients, those with injuries above the T6 level frequently experienced significant increases in blood pressure during urodynamic evaluations, indicating a risk for autonomic dysreflexia (AD).

The onset of AD was linked to bladder conditions such as uninhibited contractions and bladder distension, suggesting that while anticholinergic drugs may help, they are not always effective in preventing AD unless they cause detrusor areflexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia during urodynamics. Giannantoni, A., Di Stasi, SM., Scivoletto, G., et al.[2019]

In a study involving rats with spinal cord injury (SCI), blood flow in the femoral arteries was significantly reduced, indicating impaired vasomotor function after injury.

The research found that the expression of α1-adrenergic receptors was increased in the arterial smooth muscle of rats with SCI, which enhances their responsiveness to certain stimuli and contributes to the development of autonomic dysreflexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord injury enhances arterial expression and reactivity of α1-adrenergic receptors-mechanistic investigation into autonomic dysreflexia. Lee, JS., Fang, SY., Roan, JN., et al.[2018]

In a study of 13 pediatric patients with spinal cord injury (SCI) at or above T8 and other severe neurological disorders undergoing urodynamic studies (UDS), only two patients developed autonomic dysreflexia (AD), indicating a low prevalence in this specific population.

AD was effectively managed conservatively without major complications, and the study found that patients who experienced AD during their first UDS were at increased risk for subsequent episodes, while those who did not experience AD initially did not develop it in later tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia during urodynamics in children and adolescents with spinal cord injury or severe neurologic disease. Canon, S., Shera, A., Phan, NM., et al.[2015]

A study involving 100 individuals with chronic spinal cord injury (SCI) and 16 family members revealed significant gaps in knowledge about autonomic dysreflexia (AD), with 41% of participants unaware of the condition and 22% experiencing unrecognized symptoms.

Education on AD recognition and management is best delivered during rehabilitation by healthcare professionals, which could help reduce the risk of serious complications like cardiac and cerebrovascular disease in the SCI population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating knowledge of autonomic dysreflexia among individuals with spinal cord injury and their families. McGillivray, CF., Hitzig, SL., Craven, BC., et al.[2021]

The American Spinal Injury Association and the International Spinal Cord Society are developing new assessment criteria for evaluating autonomic function in individuals with spinal cord injury, aiming to enhance the understanding of neurological function and treatment effects.

The committee recommends assessing specific conditions related to autonomic dysfunction, including neurogenic shock, cardiac dysrhythmias, orthostatic hypotension, autonomic dysreflexia, temperature dysregulation, and hyperhidrosis, to improve clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of autonomic dysfunction following spinal cord injury: rationale for additions to International Standards for Neurological Assessment. Krassioukov, AV., Karlsson, AK., Wecht, JM., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Exploring detailed characteristics of autonomic dysreflexia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

What do physiotherapists and physiotherapy students know about autonomic dysreflexia? [2021]

3. England pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia caused by cervical stenosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Silent autonomic dysreflexia during a routine bowel program in persons with traumatic spinal cord injury: a preliminary study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Sympathetic skin responses and autonomic dysfunction in spinal cord injury. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia during urodynamics. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Spinal cord injury enhances arterial expression and reactivity of α1-adrenergic receptors-mechanistic investigation into autonomic dysreflexia. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Autonomic dysreflexia during urodynamics in children and adolescents with spinal cord injury or severe neurologic disease. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Evaluating knowledge of autonomic dysreflexia among individuals with spinal cord injury and their families. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Assessment of autonomic dysfunction following spinal cord injury: rationale for additions to International Standards for Neurological Assessment. [2022]