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.
The purpose of this study is to learn more about the regulation of the veins of the abdomen by the autonomic (involuntary) nervous system, and how this may affect high blood pressure. About 32 participants will be screened for the study. We estimate 16 will be eligible to participate in all of the study days.
Normally, the autonomic nervous system controls how much blood flows in the veins. In people with high blood pressure, however, the autonomic nervous system is changed. We think that this change may affect the way blood flows in the veins of the abdomen which may play a role in their high blood pressure.
Eligible participants with multiple system atrophy (central autonomic failure) and supine hypertension (high blood pressure while lying down) will be studied in a randomized, interventional study. During the study, you will be asked to stop taking any medication that may alter your blood pressure for up to seven days prior to the study days. If we don’t stop these medications, the results of the tests may be difficult to interpret and may fool us into believing that your autonomic system is not working well. If you cannot tolerate stopping your medications, we will restart them immediately but you will not be able to be in the study.
The purpose of the screening procedures is to learn more about the type of disease that affects your autonomic nervous system and run some safety tests to see if you qualify for this study and if it is safe for you to be in the study. Screening procedures can be performed in one or more days depending on the patient’s and investigator’s availability. You will be asked to come to the Vanderbilt Autonomic Dysfunction Center for testing.
- You will be asked questions about your health, medical history, and family health history. This interview can occur in person, over the phone, or by using questionnaires.
- You will be given a medical exam.
- We will take blood (about one tablespoon) and may also ask you for a urine sample.
- You will have an ECG (electrocardiogram, a test that measures the electrical activity of your heart).
- Your blood pressure and heart rate will be measured in these different positions.
- Your blood pressure will be measured using a cuff around your arm or finger.
- You will be asked to breathe deeply for two minutes and breathing against pressure for 15 seconds. These tests will let us know how well your involuntary nervous system is working.
Medical history information and results from any of the screening procedures obtained within the previous 6 months for other studies within this research group may be utilized.
Study Procedures: Study Day 1 and 2
The study procedures will be conducted on two separate days. On one study day, you will be given trimethaphan, a medicine that is investigational - meaning it is not approved by the Food and Drug Administration (FDA), and on the other study day, you will be given placebo (saline, a salt solution). All of the procedures on each study day will be the same. The only difference will be the drug you are given. The order of the study days will be decided at random, like the toss of a coin. You will not know which infusion you are receiving, the doctors will. Each study day will last about 3 hours.
- You will be asked to remain lying down for the procedures.
- We will wrap a blood pressure cuff around your upper arm and a special device around your finger to measure your blood pressure.
- We will apply sticky patches to the front of your body to measure changes in blood volume within your body (body impedance) and your heart rate (ECG). We will also place sticky patches on your forearm to measure the amount of blood flow to your skin.
- A small plastic tube (IV) will be placed in your arm in a vein near the crease of your elbow to give you the study medication.
- We will measure your heart’s pumping capacity (cardiac output) by studying the air you breathe through a mouthpiece connected to a bag full of air and small amounts of some inactive gases (“rebreathing test”).
- We will ask you to wear a facemask to apply a low air pressure in your airway [“continuous positive airway pressure (CPAP)”].
At the end of the procedures, the infusion of trimethaphan will be stopped and you will be monitored until blood pressure is restored to baseline values.
To be eligible to participate, you must:
- Be male or female aged 40-80 years, with possible or probable Multiple System Atrophy, as defined by Consensus Criteria.
- Have neurogenic orthostatic hypotension defined as a ≥30-mmHg decrease in SBP within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
- have supine hypertension, defined as SBP≥150 mmHg measured on two separate occasions.
- Be able and willing to provide informed consent.
You are not eligible to participate if:
- You are pregnant.
- Have a systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
- Have a history of known aortic aneurysms, thoracic, abdominal or pelvic surgery in the past 6 months.
- Have symptomatic abdominal or inguinal hernias.
- Have severe gastroesophageal reflux.
- Have had recent fractures or fissures of ribs, thoracic or lumbar spine.
- Have medical devices implanted on the abdominal wall or abdomen that would interfere with the abdominal compression.
- Have an intolerance to any increase in intra-abdominal pressure.
- You are clinically unstable coronary artery disease or major cardiovascular or neurological event in the past 6 months, and other factors which in the investigator’s opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.