Autonomic Disease

Alpha-synucleinopathies are age-related neurodegenerative disorders characterized by the build-up of alpha-synuclein in nerve cells, leading to conditions like Parkinson's 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 [18F]F-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 [18F]F-DOPA. The PET scan involves a slow injection of [18F]F-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 [18F]F-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 studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.

Researchers are studying patients with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) caused by ACTA2 genetic variants. This observational study combines a review of past medical records with ongoing collection of clinical data using standardized tools and scheduled visits. The goal is to better understand disease progression, symptoms, and related health changes over time. The study plans to enroll about 100 patients divided into different age groups or cohorts, including a retrospective cohort covering all ages. Participants are grouped into cohorts by age: infants to 6 years, children 7 to 18 years, adults 19 years and older, and a retrospective group of all ages. Patients in cohorts 1 to 3 will attend in-person clinic visits following a schedule of events. The retrospective cohort involves reviewing available medical records from birth to document disease features and developmental milestones. The study is planned for at least 3 years, with options for longer follow-up depending on funding and patient participation. During the study, data will be collected from medical records, clinical assessments, patient and caregiver reports, and wearable technology to monitor disease changes and progression. Researchers will evaluate both vascular and non-vascular symptoms and compare remote assessments with in-person performance measures. Participants may move between cohorts as they age. The study includes regular monitoring to track health status and outcomes over time, with a total participation duration of at least 3 years and possible extension.

Researchers are developing and managing the AnovaOS Network Powered Patient Registry to collect real-world patient data across various diseases globally. This registry aims to capture meaningful clinical information on diagnosis, infection course, treatments, and outcomes to enhance understanding and support future clinical trials and observational studies. The registry serves as a resource to better understand, prevent, diagnose, and treat diverse health conditions. Participants' data will be gathered through this registry, which can also be used to recruit individuals for clinical trials and observational studies on promising therapies. The registry collects ongoing information on patients' health status and treatments, enabling long-term monitoring and analysis. This observational study does not involve administering treatments but focuses on data collection and management. Participants will provide information through questionnaires or instruments, either personally or via an informed proxy, with an expected follow-up once per year. The research team will assess natural history, clinical effectiveness, safety, and quality of care over a period of five years. The registry includes patients with a wide range of conditions, and participation requires informed consent and the ability to complete follow-up data collection.

Researchers are studying Hypermobile Ehlers-Danlos Syndrome (hEDS), a connective tissue disorder that causes very flexible skin and joints, along with other tissue issues. This condition often comes with gastrointestinal and autonomic nervous system problems, such as postural orthostatic tachycardia syndrome (POTS). The study explores the link between hEDS and autonomic regulation and evaluates if two types of non-invasive vagal nerve stimulation therapies can reduce gastrointestinal symptoms in people with hEDS and POTS. It also examines how these therapies might affect stomach function and nerve signaling. The study involves two groups of participants. One group of 60 children with hEDS or Hypermobile Spectrum Disorder will participate in a four-week, randomized, double-blind trial listening to either special filtered vocal music designed to stimulate vagal nerve calming (active therapy) or regular music (sham therapy). The other group of 30 children with autonomic nervous system dysfunction will receive a six-week open-label treatment using a device called IB-Stim, which provides low voltage nerve stimulation through electrodes on the ear. Some participants may also undergo a gastric MRI scan and provide blood samples for additional research. Participants will be assessed before, during, and after therapy using questionnaires about gastrointestinal symptoms, body perception, and nerve function. The study measures changes in these symptoms and uses imaging to observe stomach motor function. Monitoring includes questionnaires and physiological tests over about six weeks of therapy. The trial runs until the end of 2026, and researchers will review outcomes like symptom improvement and nerve efficiency to understand effects of these therapies on hEDS and related autonomic issues.

Researchers are investigating autonomic dysfunction (AD) and orthostatic intolerance (OI) in patients who have undergone bariatric surgery (BS). This observational study aims to assess how common AD is after BS and to better understand the underlying causes and outcomes. Previous research has shown limited and low-quality evidence on this topic, prompting this study to improve knowledge about AD/OI following bariatric procedures. The study includes both retrospective and prospective phases. Patients who have had BS within the last 3 years or will undergo BS soon are observed to characterize the development of AD/OI after surgery. Bariatric surgeries studied include gastric bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. The study does not involve any experimental treatments but focuses on monitoring and collecting data about AD/OI symptoms and progression. Participants will provide consent and maintain follow-up with their bariatric surgery team. Researchers will evaluate the prevalence and outcomes of autonomic dysfunction at around 3 months after surgery. Data collection includes medical history, symptom tracking, and follow-up evaluations to better define AD/OI characteristics. The study will end in December 2025, allowing for thorough observation and outcome assessment over time.

This research aims to better understand disorders of gut-brain interaction (DGBI) in female children aged 11 to 18 who experience symptoms like cyclic vomiting and functional dyspepsia along with signs of autonomic nervous system (ANS) imbalance. These conditions often include disabling symptoms such as sleep disturbances, fatigue, anxiety, palpitations, and dizziness. The study focuses on the brain-gut mechanisms behind these symptoms and evaluates treatments targeting the ANS regulation through novel methods. Participants will receive personalized percutaneous electrical nerve field stimulation (PENFS) therapy applied to the external ear for six weeks. Some will also receive adjunctive gut-directed hypnotherapy through audio recordings. The study evaluates real-time ANS regulation using a new tracking software and adjusts neurostimulation parameters based on individual sensory thresholds. A subset of participants will undergo advanced MRI to assess gastric function before and after therapy. Throughout the study, participants will be monitored weekly for autonomic nervous system activity and symptom changes using patient-reported outcomes and gastrointestinal symptom severity assessments. Researchers will measure vagal efficiency and symptom response to personalize treatment. The trial includes a six-week treatment period with follow-up evaluations to assess therapy effects. Safety and symptom reporting will be carefully observed during the study period.

Researchers are investigating how the autonomic nervous system controls blood pressure and heart rate during standing and exercise in both healthy adults and people with arterial hypertension. The study focuses on understanding cardiovascular responses to exercise on a cycle ergometer and includes groups with hypertension and related conditions like orthostatic hypotension and diabetes. This observational study aims to improve knowledge of cardiovascular regulation and may help identify autonomic dysfunction earlier for better clinical care. Participants include healthy young adults aged 18 to 35 without cardiovascular disease and several subgroups of older adults with controlled arterial hypertension, with or without orthostatic blood pressure abnormalities or diabetes. All participants undergo tests such as orthostatic testing, graded exercise on a cycle ergometer, electrocardiography, and arterial stiffness measurements like pulse wave velocity. Additional vascular and hemodynamic parameters are also recorded during these procedures. During the single study visit, researchers assess heart rate variability, blood pressure response to exercise, and heart rate recovery immediately after exercise. Clinical data including lab results and ambulatory blood pressure monitoring are collected from medical records for participants with hypertension. The study monitors cardiovascular function and autonomic regulation to contribute to better understanding and management of hypertension and related conditions.

Researchers are studying patients with various autonomic neuropathies and Ehlers-Danlos syndromes, comparing them to healthy individuals at three time points: baseline, after 3 months, and after 1.5 years. The study focuses on understanding the disease progression and the underlying mechanisms, especially involving Small Fiber neuropathy. It also aims to validate the German version of the Malmö POTS Score and develop a simple diagnostic approach for outpatient care patients. Participants include groups with Postural Orthostatic Tachycardia Syndrome, hypermobile or classical Ehlers-Danlos syndromes, autoimmune autonomic neuropathies, mast cell activation syndrome, chronic fatigue, PostCOVID syndrome, and healthy controls. They receive standard treatment based on their conditions, with no experimental intervention planned. Evaluations occur at baseline, 3 months, and 18 months, including clinical and diagnostic tests. Throughout the study, participants undergo laboratory tests, questionnaires about physical and mental health and circulatory issues, attention tests, tilt table and standing tests, sweat function assessments, small fiber function testing via quantitative sensory testing, and skin biopsy to measure nerve fiber density. Researchers monitor blood pressure, heart rate, and a composite autonomic severity score at each visit. Follow-ups help track disease changes and improve diagnosis, with total participation lasting up to 18 months.

Researchers are exploring the potential of cardioneuroablation, a minimally invasive catheter ablation technique targeting cardiac ganglionated plexi, for treating significant vagally-mediated bradycardia. This condition involves abnormally slow heart rates caused by overactive vagal nerve signals. The study combines basic science and clinical investigation to address the current lack of high-level evidence on the safety and effectiveness of this therapy, aiming to establish a reliable, evidence-based treatment strategy. This approach avoids permanent device implantation and focuses on suppressing abnormal vagal activity that contributes to bradycardia symptoms like syncope and fatigue. The study randomly assigns participants to one of two groups: one receiving cardioneuroablation targeting atrial ganglionated plexi through a catheter procedure performed under local anesthesia with sedation, and the other undergoing a sham procedure without ablation or transseptal puncture. The ablation involves catheter insertion through the femoral vein, positioning in the heart guided by imaging, and sequentially ablating specific nerve clusters in the atria. The sham procedure mimics the preparation and catheter placement but does not include ablation, with participants wearing headphones and an eye mask to maintain blinding. Participants will be monitored with 24-hour ambulatory electrocardiograms at baseline and at 1, 3, 6, and 12 months post-procedure to measure average heart rate, PR interval, and heart rate variability. Quality of life will be assessed with a standardized health survey at baseline and 12 months. The study emphasizes rigorous design and standardized procedures to ensure reliable and reproducible results. Participant involvement includes multiple follow-up visits over a year to assess heart rhythm changes, symptoms, and overall wellbeing, supporting a comprehensive evaluation of the intervention's impact.