Active clinical trials for "Pure Autonomic Failure"

This study (https://pdrisk.ninds.nih.gov) will determine if people who have risk factors for Parkinson disease (PD) have biomarkers (objective ways to measure a disease process) that show that the disease process is actually going on, and if people who have abnormal biomarkers go on to develop PD during several years of follow-up. Biomarkers of Parkinson disease (PD) might identify people who are healthy now but may develop the disease later in life. Healthy volunteers and people who have certain risk factors for developing PD who are between 18 and 70 years of age may be eligible for this study. People with the following risk factors are included: Family history of PD Loss of sense of smell Fall in blood pressure when standing up REM behavior disorder (a type of sleep disturbance) Participants undergo the following tests and procedures: Screening examination Medical and neurological history and physical examination Tests or rating scales for movement, sense of smell, mood, attention, fatigue, pain, and thinking. Measurement of blood pressure and pulse rate while lying down and then standing up Blood draw for genetic testing Inpatient testing at the NIH Clinical Center for 2-3 days, including: Measurements while blowing against a resistance Measurements of blood pressure and pulse rate Blood draws for levels of various chemicals PET and MRI scanning Lumbar puncture (spinal tap) Electrocardiogram Skin electrical conduction test (test of sweat production) Skin and core temperature measurements Transcranial ultrasound (sound-wave test of the head) Follow-up testing (up to five visits in 18-month intervals) to repeat some of the tests listed above, excluding the genetic testing and spinal tap

The amount of blood flowing to the different parts of the body is regulated by the autonomic (automatic) nerves and by local factors produced by the blood vessels. Nitric oxide (NO) is one of the most important of these metabolic factors. If the production of NO is slowed or stopped the amount of blood to the different parts of the body is decreased. There is increasing knowledge that NO mechanisms are impaired in a number of medical conditions. NO function is reduced in patients with risk factors for atherosclerosis (hardening of the arteries) such as hypercholesterolemia (patients with high cholesterol), or diabetes mellitus, and is also impaired in smokers. This NO "deficiency" is believed to contribute to the greater cardiovascular risk that marks these patient populations. This study is designed to examine if endothelial nitric oxide is an important control mechanism of blood pressure under normal conditions, and if impairment of nitric oxide contributes to hypertension.

Intensive glucose control in type 1 diabetes mellitus (T1DM) is associated with clear health benefits (1). However, despite development of insulin analogs, pump/multi-dose treatment and continuous glucose monitoring, maintaining near-normal glycemia remains an elusive goal for most patients, in large part owing to the risk of hypoglycemia. T1DM patients are susceptible to hypoglycemia due to defective counterregulatory responses (CR) characterized by: 1) deficient glucagon release during impending/early hypoglycemia; 2) additional hypoglycemia-associated autonomic failure (HAAF) and exercise-associated autonomic failure (EAAF) that blunt the sympathoadrenal responses to hypoglycemia following repeated episodes of hypoglycemia or exercise as well as degrading other CR; and 3) hypoglycemia unawareness (HU), lowering the threshold for symptoms that trigger behavioral responses (e.g. eating). Thus, the risk of hypoglycemia in T1DM impedes ideal insulin treatment and leads to defaulting to suboptimal glycemic control (2). There are two approaches that could resolve this important clinical problem: 1) perfection of glucose sensing and insulin and glucagon delivery approaches (bioengineered or cell-based) that mimic normal islet function and precisely regulate glucose continuously, or 2) a drug to enhance or normalize the pattern of CR to hypoglycemia. Despite much research and important advances in the field, neither islet transplantation nor biosensor devices have emerged as viable long-term solutions for the majority of patients (3, 4). Over the past several years, our lab has explored the approach of enhancing CR by examining mechanisms responsible for HAAF/EAAF and searching for potential pharmacological methods to modulate the CR to hypoglycemia (5-11). Our work has led to a paradigm shift in the field of hypoglycemia, exemplified by the novel hypothesis and published experimental data supporting a role for opioid signaling that resulted in the initiation of exploratory clinical trials by other research groups.

The purpose of this study is to determine what corticosteroid receptor (and the dose of) is responsible for cortisol inducing hypoglycemia associated autonomic dysfunction in Type 1 DM. Specifically, we aim to determine whether stimulating the type 1 corticosteroid receptor (via fludrocortisone), the type 2 corticosteroid receptor (via dexamethasone), or both causes hypoglycemia associated autonomic dysfunction in Type 1 DM.

The purpose of this study is to identify 15 patients with autonomic failure and obtain blood samples for RNA from those participants and 15 control subjects within the same age range. The stabilized blood samples, along with a limited data set, will be shipped to Western Michigan University where the actual laboratory analysis (a separate study) of the samples will take place. Unique genetic inscriptions, called gene expression signatures, are currently being identified for many diseases, including neurological diseases. The secondary goal of this study is to support the research being done at WMU and they try to look for MSA-specific signs are present in whole blood samples of MSA patients at late-stages of the disease. This is a pilot study that has a long term goal (through additional studies) a MSA-specific gene expression signature for the development of a diagnostic test for this disease that can be used in the future. Other patient groups with autonomic failure, characterized by significant drop in blood pressure on standing, will also be included in this study, to look for similar genetic inscriptions. This pilot study is expected to last for 2 years. The investigators at WMU will need some de-identified health Information about the subjects, including their age at diagnosis, age (when sample drawn) and list of their medications