Postural Orthostatic Tachycardia Syndrome (POTS)

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 evaluating the safety and effectiveness of oral Apabetalone combined with background dapagliflozin treatment for up to 12 weeks in adults with type 2 diabetes mellitus (T2DM) who have experienced probable or confirmed COVID-19 infection. Participants must have symptoms of Long COVID lasting at least 2 months within 3 months from the start of COVID-19, which cannot be explained by other diagnoses. This phase II, open-label multicentre trial aims to better understand treatment options for this group of patients. Participants will take oral Apabetalone 100 mg capsules twice daily with meals while continuing their daily dapagliflozin 10 mg therapy for diabetes. The study involves seven in-person clinic visits where data will be collected to assess the treatment's effects. After screening and consent, eligible participants begin Apabetalone treatment on Day 1 and continue it at home under study supervision. During the trial, participants will undergo various assessments including symptom evaluations and functional status tools related to Long COVID. The primary outcome is the patient acceptable symptom state at 90 days. Secondary measures include fatigue, dyspnea, and post-exertional malaise assessments. Safety and adherence will be monitored throughout, with the total study duration covering treatment and follow-up visits over approximately 12 weeks.

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.

Researchers are studying the safety and effectiveness of Anktiva, also known as Nogapendekin Alfa Inbakicept (NAI), in people experiencing Long COVID, which means continuing symptoms after a COVID-19 infection has ended. This Phase 2 study aims to understand how this treatment may help patients with persistent symptoms that affect their quality of life. The study is sponsored by ImmunityBio, Inc. and focuses on adults aged 18 to 70 years with confirmed Long COVID symptoms lasting at least 60 days. Participants will receive 600 micrograms of Anktiva administered by a subcutaneous injection. The study is a single-arm trial, meaning all participants receive this treatment without comparison to a placebo or other drug. Treatment and monitoring will occur over approximately 75 days, including the time after the final dose to track safety and response. There are no placebo groups or blinding in this research. During the study, participants will attend visits for assessments including blood tests, vital signs monitoring (temperature, heart rate, blood pressure, respiratory rate, oxygen saturation), and symptom evaluations. Researchers will monitor for any treatment-related side effects or serious adverse events up to 30 days after the last dose. They will also assess changes in lymphocyte counts and other laboratory values. Participants should expect regular study visits and evaluations for safety and effectiveness over the treatment period.

Researchers are comparing the immediate heart and lung responses and personal feelings during a single exercise session in people who had Covid-19. The study focuses on those with ongoing symptoms after Covid-19 infection, known as Post-Acute Covid-19 Syndrome, and those who had Covid-19 but do not have persistent symptoms. This research aims to understand these differences using physical and perceptual measures. Participants will take part in two sessions: one where they exercise and another where they simply rest while seated. The exercise session lasts about 45 minutes and includes aerobic activities like jumping jacks and walking, followed by strength exercises targeting main muscle groups, and finishing with stretching. The control session lasts 60 minutes with participants remaining seated. During these sessions, researchers will measure blood pressure, heart rate variability, oxygen levels, vascular function, and breathing capacity before, during, and after exercise or rest. Participants' feelings and perceptions will also be recorded regularly. These measurements will help evaluate how the body and mind respond acutely to exercise in people with or without ongoing Covid-19 symptoms. The study is randomized and includes safety monitoring for cardiovascular risk.

Researchers are evaluating the effectiveness of two antiviral drugs, Paxlovid and Veklury, in preventing long-term cardiovascular problems following COVID-19 among hospitalized adults. This study, called the DEFEND trial, will be the first of its kind to focus on cardiovascular post-acute sequelae of SARS-CoV-2 in this patient group. It is a pilot, randomized, placebo-controlled trial designed to also help plan a larger future study by testing recruitment feasibility and accuracy of hospital outcome data. Participants will be randomly assigned to receive either Paxlovid orally twice daily for 5 days or Veklury intravenously once daily for 5 days, alongside standard care, or a matching placebo on the same schedule. The trial will enroll adults aged 18 or older who have tested positive for SARS-CoV-2 within 5 days of hospital admission and are not requiring supplemental oxygen. The study will recruit about 118 participants across four hospitals in Ontario, followed by a 12-month observation period after treatment. During the study, researchers will monitor participants from the time of screening through enrollment and track major cardiovascular events such as stroke, heart failure, venous thromboembolism, diabetes, or death within one year. They will also validate hospital data accuracy, assess reinfection, ICU admission, and drug safety within 90 days of the initial COVID-19 test. The trial includes thorough follow-up and safety monitoring over the full year to understand the long-term cardiovascular outcomes related to COVID-19 and the potential preventive effects of the antiviral treatments.

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.