Autonomic Dysregulation

Spinal anesthesia-induced hypotension is a common and significant complication affecting up to 50-80% of pregnant women undergoing elective cesarean section. This trial evaluates whether a brief 5-minute mindfulness-based breathing exercise given just before spinal anesthesia can influence blood pressure changes during surgery. The study compares this breathing technique to standard care in pregnant women aged 18 to 45 years scheduled for elective cesarean delivery. Participants will be randomly assigned to either perform the mindfulness-based breathing exercise or receive standard preoperative care. The breathing exercise involves slow diaphragmatic breathing at about six breaths per minute, guided by a trained anesthesiologist or nurse, with mindful repetition of the phrase My body is relaxing as I exhale. Both groups receive spinal anesthesia with specific medications, and careful monitoring of heart rate and blood pressure is performed. During the study, participants will be closely observed for changes in systolic blood pressure and heart rate within 10 minutes after spinal anesthesia. Anxiety levels, incidence of early hypotension, and medication use to support blood pressure will also be measured. The trial includes standard monitoring such as ECG and oxygen saturation, with safety and response data collected throughout the procedure. Participants involvement includes a short breathing exercise or equivalent wait time before anesthesia, with follow-up assessments during surgery.

The trial investigates the treatment of postinduction hypotension, a common complication during emergency abdominal surgery caused by factors like sepsis and low blood volume. This condition can lead to serious organ damage, so preventing and managing it quickly is important. The study compares two doses of norepinephrine bolus5 mcg and 10 mcgto find the best approach for treating low blood pressure in this setting. Participants will be randomly assigned to receive either a 5 mcg or 10 mcg norepinephrine bolus if their mean arterial pressure drops below 65 mmHg during surgery. The drug is prepared by diluting norepinephrine to a concentration of 10 mcgmL, then further diluted for dosing. If blood pressure does not improve within 2 minutes, the bolus may be repeated up to three times, followed by an infusion if needed. Fluid status will be assessed using leg raising maneuvers and fluid boluses before surgery, and heart rate and blood pressure will be monitored every 2 minutes for 30 minutes after skin incision. During the study, participants will undergo close blood pressure and heart rate monitoring at specified intervals. Researchers will measure the success of managing hypotension from anesthesia induction until 30 minutes after surgery begins. They will also assess the time and extent of low blood pressure, episodes of slow heart rate, and high blood pressure. The entire participation period covers the time from anesthesia induction to 30 minutes post-incision, focusing on immediate treatment response and safety under surgical conditions.

Alpha-synucleinopathies are age-related neurodegenerative disorders characterized by the build-up of alpha-synuclein in nerve cells, leading to conditions like Parkinsons disease, Multiple System Atrophy, and Dementia with Lewy Bodies. Pure Autonomic Failure is a related condition affecting the peripheral autonomic nervous system and may signal risk for developing central nervous system synucleinopathies. Researchers aim to identify biomarkers, especially changes in dopamine production in key brain areas, to predict progression from peripheral to central disease. Participants receive a radiolabeled drug called 18FF-DOPA, which is used in PET scans to study dopamine activity in the brain. Before the PET scan, patients take oral doses of carbidopa and entacapone to enhance imaging quality by reducing peripheral metabolism of 18FF-DOPA. The PET scan involves a slow injection of 18FF-DOPA followed by about 95 minutes of serial brain imaging to observe dopamine-related changes. During the study, participants undergo clinical exams to confirm diagnosis and receive the PET imaging procedure. Researchers measure differences in 18FF-DOPA uptake across patient groups 95 minutes after imaging starts to assess dopamine function. The study includes patients with autonomic failure, possible synucleinopathies, and healthy adults aged 18 and older. The study is designed to monitor safety and gather detailed imaging data over the scan period.

Researchers are evaluating a combined sleep promotion and cognitive training intervention to help improve cognitive function in older survivors of intensive care units ICU. This study focuses on adults aged 60 and older who are at high risk for delirium and cognitive decline similar to mild Alzheimers disease after ICU discharge. The study aims to assess whether these interventions can reduce the risk of developing Alzheimers disease and related dementias by addressing sleep deficiency, inactivity, and circadian rhythm disturbances common in ICU survivors. Participants will be randomly assigned to one of four groups a combination of nighttime sleep promotion using earplugs and eye masks plus daily 30-minute computerized cognitive training sessions cognitive training alone sleep promotion alone or an active control group receiving educational modules on brain health. The interventions last up to seven days following ICU discharge, with cognitive training sessions scheduled based on individual circadian rhythms measured by a wearable sensor. During the study, participants will be monitored using body temperature sensors to optimize the timing of cognitive training. Researchers will assess cognitive function, including executive function and working memory, at several time points within seven days after hospital discharge, and at one, six, and twelve months follow-up. The study also examines how sleep and activity may influence cognitive outcomes, with safety and ongoing care monitored throughout the study period, which concludes in May 2027.

Researchers are evaluating the effects of CST-3056 on symptoms and signs of neurogenic orthostatic hypotension nOH, a condition that causes a significant drop in blood pressure upon standing. This Phase 2 study focuses on people diagnosed with symptomatic orthostatic hypotension due to Parkinsons disease or pure autonomic failure. The study aims to better understand how CST-3056 impacts standing blood pressure and orthostatic symptoms in these subjects. Participants will receive single oral doses of CST-3056 once daily for five days, including an optimal dose day determined from earlier doses based on standing blood pressure and tolerability. The study also includes a placebo group receiving a single dose on one day. Subjects must discontinue other treatments using alpha-1 adrenergic receptor agonists for at least one day before key assessments and dosing. The dosing is conducted in a single-blind, sequential manner. During the study, participants will be closely monitored for changes in standing and seated blood pressure, orthostatic symptom severity using the Orthostatic Hypotension Symptom Assessment OHSA, and responses to head-up tilt table testing. Follow-up occurs 3 to 7 days after discharge via telephone to review health status and report any adverse events. The total study duration per participant includes screening, treatment over five days, and a safety follow-up call after discharge.

Researchers are evaluating pyridostigmine compared to a placebo for treating postural tachycardia syndrome POTS, a condition characterized by rapid heart rate and symptoms like weakness and lightheadedness when standing. This phase 2 study aims to see if pyridostigmine can improve heart rate and stabilize blood pressure in people with POTS. The study is double-blind and placebo-controlled, meaning neither participants nor doctors know who receives the active drug or placebo during the trial. Participants will be randomly assigned to one of two groups one taking 180 mg of time-release pyridostigmine daily, and the other taking a placebo capsule daily, both for 3 days. The study includes two visits to the outpatient General Clinical Research Center. The first visit lasts about 3 hours, and the second visit occurs 2 days later, lasting about 2 hours. During these visits, various tests and procedures assess autonomic and cardiovascular function. During each visit, participants will undergo a medical and neurological exam, height and weight measurement, and complete questionnaires about autonomic symptoms. Tests include an autonomic reflex screen with sweat gland response, cardiovascular recordings, the Valsalva maneuver, and a head-up tilt test. Blood samples will be taken to measure hormone levels while lying down and after standing. Researchers will measure changes in orthostatic symptoms using the Composite Autonomic Symptom Scale and monitor heart rate and plasma norepinephrine changes. Safety and response will be closely observed throughout the short study period.

This research aims to evaluate whether advanced hemodynamic monitoring using the MostCare system provides better detection and management of hemodynamic events requiring intervention compared to standard monitoring alone during propofol sedation for ERCP procedures. ERCP is a less invasive procedure used to treat biliary and pancreatic duct disorders, often performed in elderly patients who face challenges in anesthesia and sedation due to hemodynamic fragility and other health conditions. The study focuses on improving perioperative hemodynamic management to maintain adequate organ perfusion and oxygen delivery during these procedures. Participants will be assigned to one of two groups one receiving standard monitoring during ERCP sedation, which includes non-invasive blood pressure, electrocardiography, peripheral oxygen saturation, and bispectral index monitoring and the other receiving standard monitoring plus advanced hemodynamic monitoring with the MostCare system. The MostCare device uses arterial waveform analysis to continuously assess parameters like cardiac output, stroke volume, and systemic vascular resistance. Sedation will be provided with midazolam and propofol following the study protocol. During the study, participants will be monitored from the start of sedation until the end of the ERCP procedure to record hemodynamic events that require clinical intervention. Researchers will collect advanced and standard monitoring data to compare outcomes. The primary measure is the number of such events during the procedure. The study is randomized and parallel in design, with no masking, and participants health and procedure tolerance will be closely observed throughout the trial period.

The trial investigates whether the perfusion index PI can reliably predict changes in systolic blood pressure SBP in adults with spinal cord injury SCI during a controlled cool temperature challenge. The study involves participants aged 18 to 75 years with SCI at neurological levels C4-T12 graded as ASIA Impairment Scale A or B motor complete, along with healthy age- and gender-matched able-bodied controls. Researchers aim to understand the relationship between PI and SBP changes, which may help clarify blood pressure instability after SCI and contribute to developing wearable monitoring devices. Participants in both groups undergo a non-invasive cool thermal challenge in a climate-controlled chamber at 18C 64.4F for up to 90 minutes, after a 10-minute baseline period at 27C 80F. They wear shorts and a T-shirt while seated in a wheelchair. Continuous measurements of PI, blood pressure, and other vital signs are recorded using sensors attached to the skin throughout the warm baseline and cool challenge phases. During the study, participants will have temperature sensors taped to their forehead and pulse oximeters placed on their ear, finger, and toe to measure PI and beat-to-beat blood pressure. Measurements are taken while seated in a wheelchair for 10 minutes in a warm room and then up to 90 minutes in a cool room. The primary outcomes are continuous recordings of PI and SBP during these phases. This research may support the development of wearable devices for early detection and management of blood pressure fluctuations in persons with SCI.

Researchers are investigating the risk of low blood pressure hypotension after anesthesia induction in high-risk patients with serious health conditions, classified as American Society of Anesthesiologists ASA physical status 3 or 4. This study compares a new method called target-controlled infusion TCI of propofol to the standard manual anesthesia induction. Previous research showed TCI may cause less hypotension in general patients, and this trial continues that work focusing on patients at higher risk. The study involves two groups of patients undergoing major elective surgery. One group receives manual anesthesia induction where propofol is given at a fixed dose based on weight over 1-2 minutes, aiming for a hypnosis level measured by bispectral index BIS of 35-60. The other group receives TCI induction where the propofol concentration is computer-controlled and adjusted to maintain a hypnosis level measured by BIS of 35-55. Both groups are monitored using a pressure recording analytical method PRAM device to track heart and blood vessel function during and after anesthesia induction. Participants will be monitored closely from one minute before induction to ten minutes after to measure blood pressure and heart function parameters including systolic, diastolic, and mean arterial pressures. Additional heart and circulation data such as arterial elastance, stroke volume variation, and cardiac output are recorded to predict and understand hypotension. This detailed monitoring aims to compare the effects of TCI and manual induction on blood pressure stability in these high-risk patients during anesthesia.

Researchers are studying the impact of monitoring cerebral autoregulation function using regional cerebral oxygen saturation on postoperative neurological complications in patients undergoing carotid endarterectomy CEA. This surgery treats symptomatic narrowing of the extracranial internal carotid artery but carries a risk of silent strokes detected by MRI shortly after the operation. The study aims to see if real-time monitoring of cerebral oxygen index, which reflects autoregulation, can reduce ischemic brain injury around the time of surgery. Participants are randomly assigned to one of two groups. In the autoregulation group, anesthesiologists maintain the cerebral oxygen index below 0.3 by adjusting blood pressure with norepinephrine or phenylephrine infusions or by modifying oxygen and carbon dioxide levels to improve brain oxygen saturation. In the routine care group, anesthesiologists do not see the cerebral oxygen index and manage blood pressure within 20% of baseline using similar vasoactive drugs, while keeping carbon dioxide and oxygen levels within standard ranges. During the study, participants are evaluated for cerebral ischemic events within 3 days after surgery, with additional assessments including delirium during the first 3 days, cognitive tests before surgery and about 4 to 5 days after surgery, and pain levels at 24, 48, and 72 hours post-surgery. The study enrolls adults aged 18 to 80 scheduled for elective CEA and monitors them closely with brain oxygenation and clinical assessments to understand how cerebral autoregulation management affects recovery and complications.