(Aim 2 of RDCRN Project 2)
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 effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure when standing up), on the veins of the abdomen of patients with autonomic failure.
- Multiple System Atrophy (MSA)
- Pure Autonomic Failure (PAF)
- Parkinson’s Disease
Finding a reliable, accessible and inexpensive biomarker for neurodegenerative disorders is an urgent priority. A suitable biomarker could improve the accuracy of diagnosis, identify patients in the early stages of an autonomic disease and provide improvements in clinical practice and increase the development of novel treatments.
Primary autonomic failure (AF) is a rare neurodegenerative disease characterized by deposits of alpha-synuclein (protein found in the brain) affecting the autonomic nervous system. These deposits can form glial cytoplasmic inclusions impairing central autonomic neural pathways (multiple systems atrophy) or neuronal Lewy bodies affecting peripheral autonomic fibers (pure autonomic failure). Abnormalities in blood pressure regulation are among the most prominent features of AF, as evidenced by both orthostatic hypotension and supine hypertension (high blood pressure while lying down). The purpose of this study is to learn more about the effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure when standing up).
The research objectives are:
- To compare the effects of midodrine and droxidopa on stroke volume during head-up tilt.
- To determine whether midodrine or droxidopa combined with abdominal compression has an additive pressor effect during head-up tilt.
This is a randomized, double-blind, 2-arm parallel group (midodrine vs. droxidopa) interventional study. About 34 participants will be screened for the study. We estimate that 30 patients (15 in the midodrine group and 15 in the droxidopa group) will be eligible to participate in all of the study days. Participants ages 40 – 80 years of age with possible or probable Multiple System Atrophy, Pure Autonomic Failure or Parkinson disease with mild to moderate orthostatic hypotension may be able to participate. This study will be conducted at Vanderbilt University. This study consists of 2 parts: two screening days, and two testing days. There will be a rest day between the two testing days. The study will take 5 days total.
During the screening days, you may be asked to:
- Answer questions and complete questionnaires about your health, medical history and family health history. We may look at your medical records so that we can collect information about your medical history.
- Have a Medical Exam
- Have your blood taken (about 3 tablespoons)
- Provide a urine sample
- Have an electrocardiogram (test that measures the electrical activity of your heart)
- Participate in a tilt table test (a motorized table with a footboard that moves you to an upright position without you having to use your muscles to stand)
During the testing days, you will be given the active medication on one day and the placebo on the other. On each study day, there will be 2 tilt table tests that will be 3 hours apart. You will also have an electrocardiogram. A standard blood pressure cuff may be placed around your abdomen to measure your blood pressure.
To be eligible to participate, you must:
- Be 40-80 years old.
- Have possible or probable Multiple System Atrophy, Pure Autonomic Failure or Parkinson’s disease.
- Have neurogenic orthostatic hypotension.
- Able and willing to provide informed consent.
You are not eligible to participate if:
- Have supine hypertension.
- 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.