Active clinical trials for "Autonomic Dysreflexia"

The purpose of this study is to investigate the impact of 200 U intradetrusor injected OnabotulinumtoxinA (Botox®, Allergan, Inc.) (20 sites, trigone sparing) for neurogenic detrusor overactivity (NDO) and its role on reducing autonomic dysreflexia (AD) in those with chronic, traumatic spinal cord injury (SCI). In clinical practice, urinary bladder dysfunctions are commonly associated with episodes of AD. If AD is misdiagnosed or poorly managed, it may result in myocardial infarction, stroke, seizure, intracerebral hemorrhaging or even death. Reducing AD would dramatically improve the health and well-being of Canadians with SCI, and positively impact health care costs. There are an estimated 7,343 hospital re-admissions due to SCI-related conditions in Canada every year, with an estimated 5-year cost of $661 million. Reducing hospital re-admissions for secondary complications of SCI by only 10% over this time period could result in a costs savings of $66 million for Canada. Considering these statistics, the present study could be a first attempt to evaluate the economic impact of using Botox® to manage the urinary bladder following SCI. We will be able to examine its impact on episodes of AD and consequently calculate the cost saving for the Canadian health system. A significant number of individuals with SCI will require frequent emergency room visits due to episodes of uncontrolled AD that originate predominately from the urinary bladder. There is clinical evidence demonstrating that costs of bladder management following SCI will depend on the understanding of the volumes that the urinary bladder can safely hold. This is one of the positive outcomes that have been established in previous trials of Botox® therapy for the neurogenic bladder. Hypothesis: 200 U of intradetrusor injected Botox® (20 sites, trigone sparing) for neurogenic bladder detrusor hyperreflexia will decrease the severity of AD in individuals with SCI one month following treatment.

Sexuality is a high rehabilitative priority for persons following a spinal cord injury (SCI). Sexual acts can lead to autonomic dysreflexia (AD), dangerous consequences such as a sudden increase in blood pressure, severe headache, sweating above the level of the lesion and low heart rate to name a few. Ejaculation in men can provoke these significant symptoms and therefore men and women may refrain from a sexual life and biological parenthood. Adalat is the most common antihypertensive used in fertility clinics to reduce the incidence of AD. It dramatically reduces blood pressure and, therefore, results in side effects such as dizziness, fatigue and weakness. The investigators hypothesize that Minipress® (prazosin HCL), a blood pressure medication, which has a slower and less abrupt suppressive effect on blood pressure, would be a safe, effective and more appropriate medication for use in the outpatient sperm retrieval clinic and potentially for private use.

The purpose of this research study is to determine if DBS is a feasible, safe and effective therapy for pain and autonomic dysreflexia after spinal cord injury.

Despite being studied less than half as frequently, autonomic dysfunction is a greater priority than walking again in spinal cord injury. One autonomic condition after spinal cord injury is orthostatic hypotension, where blood pressure dramatically declines when patients assume the upright posture. Orthostatic hypotension is associated with all-cause mortality and cardiovascular incidents as well as fatigue and cognitive dysfunction, and it almost certainly contributes to an elevated risk of heart disease and stroke in people with spinal cord injury. In addition, autonomic dysfunction leads to bladder, bowel, sexual dysfunctions, which are major contributors to reduced quality and quantity of life. Unfortunately, the available options for treating this condition, are primarily limited to pharmacological options, which are not effective and are associated with various side effects. It has been recently demonstrated that spinal cord stimulation can modulate autonomic circuits and improve autonomic function in people living with spinal cord injury. Neuroanatomically, the thoracolumbar sympathetic pathways are the primary spinal cord segments involved in blood pressure control. Recently, a pilot study has been published demonstrating that transcutaneous spinal cord stimulation of thoracolumbar afferents can improve cardiovascular function. However, some studies have shown that lumbosacral transcutaneous spinal cord stimulation can also elicit positive cardiovascular effects. Therefore, there is no consensus on the optimal strategy in order to deliver transcutaneous spinal cord stimulation to improve the function of the autonomic system, and it may be that lumbosacral (i.e. the stimulation site being used most commonly for restoring leg function is sufficient). Another key knowledge gap in terms of transcutaneous spinal cord stimulation is whether or not the current is directly or indirectly activating these spinal circuits. Last but not least, the effects of epidural spinal cord stimulation on the function of cardiovascular, bladder, bowel and sexual system in spinal cord injury have been investigated in no study yet. AIMS AND HYPOTHESES: Aim 1. To examine the effects of short-term (one session) transcutaneous spinal cord stimulation on the frequency and severity of episodes of orthostatic hypotension/autonomic dysfunction, and bladder, bowel, and sexual functions. These effects will be compared at two sites of stimulation. Hypothesis 1.1: Short-term transcutaneous mid-thoracic cord stimulation will mitigate the severity and frequency of orthostatic hypotension/autonomic dysfunction. Hypothesis 1.2: Lumbosacral transcutaneous spinal cord stimulation will improve bladder, bowel, and sexual functions. Aim 2. To examine the effects of long-term (one month) transcutaneous spinal cord stimulation on the severity and frequency of orthostatic hypotension/autonomic dysfunction. Hypothesis 2.1: Long-term stimulation of the mid-thoracic cord will result in sustained improvements in mitigated severity and frequency of orthostatic hypotension/autonomic dysfunction that is not dependent on active stimulation. Hypothesis 2.2: Long-term lumbosacral transcutaneous spinal cord stimulation will result in sustained improvements in bowel, bladder, and sexual function that is not dependent on active stimulation. Aim 3: To examine the effects of short-term (one session) epidural spinal cord stimulation on the severity and frequency of orthostatic hypotension/autonomic dysfunction, and bladder, bowel, and sexual functions. Hypothesis 3.1: Epidural spinal cord stimulation will mitigate the severity and frequency of orthostatic hypotension/autonomic dysfunction and improve bladder, bowel, and sexual function. Hypothesis 3.3: There is no significant difference between immediate effects of lumbosacral transcutaneous spinal cord stimulation and epidural spinal cord stimulation on bladder, bowel, and sexual function. For aim 1, 14 participants with spinal cord injury and no implanted electrodes on the spinal cord will be recruited. Participants will randomly receive one-hour stimulation under each of the two stimulation conditions in a crossover manner: Mid-thoracic and Lumbosacral. For aim 2, 28 individuals with spinal cord injury and no implanted electrode will be pseudo-randomized (1:1) to one of two stimulation sites. Participants will receive one-hour stimulation, five sessions per week for four weeks. Cardiovascular and neurological outcomes will be measured before the first stimulation session and after the last stimulation session. For aim 3, 4 participants with spinal cord injury with implanted electrodes on the spinal cord will be recruited to study the immediate effects of invasive epidural spinal cord stimulation. All outcomes will be measured in two positions: a) Supine, b) ~ 70° upright tilt-test. Additionally, bowel, bladder, and sexual functions in project 2 will be assessed weekly.

This study looks to characterize autonomic nervous system dysfunction after spinal cord injury and identify the potential role that transcutaneous spinal cord stimulation may play at altering neuroregulation. The autonomic nervous system plays key parts in regulation of blood pressure, skin blood flow, and bladder health- all issues that individuals with spinal cord injury typically encounter complications. For both individuals with spinal cord injury and uninjured controls, experiments will utilize multiple parallel recordings to identify how the autonomic nervous system is able to inhibit and activate sympathetic signals. The investigators anticipate that those with autonomic dysfunction after spinal cord injury will exhibit abnormalities in these precise metrics. In both study populations, transcutaneous spinal cord stimulation will be added, testing previously advocated parameters to alter autonomic neuroregulation. In accomplishing this, the investigators hope to give important insights to how the autonomic nervous system works after spinal cord injury and if it's function can be improved utilizing neuromodulation.

This is a preliminary study of the antihypertensive drug mecamylamine, used in the specific circumstance of hypertension caused by autonomic dysreflexia (AD), a condition that affects people with spinal cord injury (SCI). Initially, mild sensory stimulation of subjects' legs is used to intentionally provoke AD, as reflected by blood pressure elevation during such stimulation. In subsequent testing sessions, mecamylamine is given prior to sensory stimulation, to show the effect of the drug on preventing these AD-related blood pressure elevations.