Autonomic Disorders Consortium

Research Studies

6106: The phenotype and natural history of primary autonomic disorders

Status: Recruiting

Study Summary

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.

For Diseases:

Background

Primary autonomic disorders are a group of diseases that usually begin in adulthood with the inability to stand because of dizziness, lightheadedness and fainting. Symptoms are the result of a dysfunction in the autonomic nerves that regulate blood pressure and heart rate, and are either related to the accumulation of abnormal protein deposits and a primary neurodegenerative process (like Parkinson disease, pure autonomic failure, dementia with Lewy bodies and multiple system atrophy), secondary to genetic abnormalities (dopamine-beta-hydroxylase deficiency), an autoimmune process (autoimmune ganglionopathy), or because of a direct injury to the nerves involved in buffering blood pressure fluctuations (acquired baroreflex failure). Furthermore, there are a group of disorders that are characterized by disabling orthostatic intolerance but no orthostatic hypotension, such as the postural tachycardia syndrome (POTS) in which the underlying cause is unclear. The purpose of this study is to characterize the clinical features and biological markers of the different types of primary autonomic disorders and better understand how these disorders evolve over time. The study will involve a series of follow-up visits to Centers participating in the Autonomic Disorders Consortium (ADC).

About this Study

Studying primary autonomic disorders poses special research challenges, primarily because these disorders are rare and affect only a small number of patients. Because the medical literature often consists of single case reports or small case series, good clinical descriptions of the features and clinical evolution of many rare autonomic diseases are lacking. The Autonomic Disorders Consortium was established with the objective of combining the medical expertise of leading autonomic sites within the United States to develop a clearer understanding of primary autonomic disorders, with the hope of developing new treatments and providing better guidance and recommendations for patient care to the medical community.

The first specific aim of this project is to create a database of patients with primary autonomic disorders that will include all their clinical features. We will use a comprehensive, integrated approach that will combine standardized clinical, physiological and biochemical studies to characterize the features of rare autonomic disorders, including disorders that are already known and others still undiscovered. This database will also allow us to identify adequate candidates for the therapeutic trials and natural history study (Specific Aim 2 of this project) of the Rare Diseases Clinical Research Network (RDCRN) Autonomic Disorders Consortium (ADC).

The second specific aim of this project is to identify patients with neurogenic orthostatic hypotension (NOH) i.e., a fall in blood pressure on standing as a result of autonomic nerve dysfunction. These participants will be followed in a 5 year longitudinal observational study with yearly assessments to characterize how these diseases evolve over time. We will determine whether the disease process always damages neurons in the brain (resulting in a movement disorder and/or signs of dementia) or can, in certain cases, remain confined to the autonomic nerves outside the brain. Finally, we will study whether certain tests can actually predict the development of different disorders associated with NOH.

At each visit you will be asked to:

  • Give details about your medical problems
  • Have a physical examination
  • Have a neurological exam with an assessment of your cognitive skills
  • Fill out questionnaires about your symptoms, sleep problems and life
  • Have an electrocardiogram
  • Give blood (4 teaspoons)
  • Give a sample of urine
  • Undergo a series of standardized autonomic tests in which your blood pressure and heart rate are recorded while laying flat, standing upright on a tilt table and during different breathing exercises.
  • Recognize smells

We will also look at your medical records so that we can collect information about your medical history, problems you may have during sleep and the structure of your heart.

The number of office visits you will be asked to attend will depend on your diagnosis. If you have orthostatic hypotension and problems with movement, you will not need to come in for annual office visits and we will follow you by phone instead. Your doctor will provide you with details as to your level of participation.

Targeted Enrollment

To be eligible to participate, you must:

  • Have been referred to any of the participating consortium sites with orthostatic intolerance (OI), defined as symptoms of dizziness or lightheadedness in the standing position that disappear when supine in whom all non-autonomic causes have been ruled out. It should be noted that orthostatic intolerance can occur with or without orthostatic hypotension (OH).
  • Be aged 18 or over

You are not eligible to participate if:

  • Diabetes (type 1 and type 2) according to the American Diabetes Association criteria
  • Congestive heart failure
  • Lupus or other collagen vascular disease
  • Systemic illness thought, in the investigator’s opinion, to be responsible for the orthostatic intolerance
  • Drug-induced orthostatic hypotension (i.e., the use of alpha-blockers, diuretics, tricyclic antidepressants or others thought by the investigator to play an important role in the patient’s orthostatic hypotension)
  • Isolated vasovagal syncope

To be eligible to participate in the natural history study, you must:

  • Orthostatic hypotension (defined fall in systolic blood pressure > 20 mmHg and a fall in diastolic blood pressure >10 mmHg)
  • Lack of blood pressure "overshoot" during phase IV of a Valsalva maneuver (i.e., after release of the strain). Lack of overshoot means that blood pressure is not above baseline levels within 10 seconds after release of the Valsalva strain.

You are not eligible to participate if:

  • You have non-neurogenic orthostatic hypotension (i.e., orthostatic hypotension which in the investigator’s opinion is the result of another "non-neurological" factor, including dehydration, severe anemia or drug-induced)

How to participate

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation

Massachusetts

Minnesota

New York

Tennessee

 

Be notified when new locations open!

Join the Contact Registry for Pure Autonomic Failure (PAF)