Autonomic Failure, Multiple System Atrophy, Neurogenic Orthostatic Hypotension, Parkinson Disease, Pure Autonomic Failure
Conditions
Keywords
midodrine, abdominal binder, splanchnic circulation, arterial stiffness
Brief summary
The purpose of this study is to learn more about the effects of abdominal compression and the medication midodrine, two interventions used for the treatment of orthostatic hypotension (low blood pressure on standing), on hemodynamic markers of cardiovascular risk. The study will be conducted at the Vanderbilt University Medical Center and consists of a screening and 2 testing days, one with abdominal compression and one with midodrine. The total length of the study will be about 5 days.
Detailed description
The study includes up to 5 days spent in the Vanderbilt University Medical Center, at least one day of screening tests, followed by 2 study days. Screening tests include a physical examination and history, routine safety laboratory assessments, and testing of the autonomic nervous system. Medications affecting blood pressure and the autonomic nervous system such as pressor medications will be withdrawn for at least 5 half-lives before studies, except for fludrocortisone. Other medications will be held constant throughout the study. Eligible participants will then be studied on two separate days in random order: one day with midodrine combined with sham abdominal compression, and one day with abdominal compression combined with a placebo pill. On each study day, participants will be instrumented to measure blood pressure, heart rate, hemodynamic parameters, segmental impedance, and markers of cardiovascular risk. A baseline tilt table test will be performed to obtain supine and upright baseline measurements, including the assessment of orthostatic symptoms. Participants will then receive a single oral dose of placebo or midodrine, and a deflated binder will be placed around the abdomen. Thirty to sixty minutes later, a second tilt table test will be done with sham or active abdominal compression. Outcome measurements will be repeated in the supine and upright positions. At the end of the second tilt table test, the investigators may also assess splanchnic venous capacitance.
Interventions
DRUGMidodrine
Midodrine 5-10 mg, single oral dose
DRUGPlacebo pill
single oral dose
DEVICEAbdominal compression
abdominal compression up to 40 mmHg during head-up tilt
DEVICEsham compression
Sham abdominal compression during head-up tilt
Sponsors
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
placebo pill and sham abdominal compression will be used
Intervention model description
Randomized, single-blind, crossover
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects, age 40-80 years, with autonomic failure including pure autonomic failure, multiple system atrophy and Parkinson disease. * Neurogenic orthostatic hypotension, defined as a ≥20-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. * Patients who are willing and able to provide informed consent
Exclusion criteria
* Pregnancy. * Patients with any contraindication or intolerant to abdominal compression including history of aortic aneurysms, thoracic, abdominal or pelvic surgery within 6 months of study participation; symptomatic abdominal or inguinal hernias; severe gastrointestinal reflux; recent fractures or fissures of ribs, thoracic or lumbar spine; medical devices implanted on the abdominal wall or abdomen that would interfere with the abdominal compression. * Pre-existing sustained supine hypertension ≥180/110mmHg * Bedridden patients or those who are unable to stand due to motor impairment or severe OH. * Patients who cannot tolerate the medication withdrawal, defined as those who are unable to stand for at least one minute after the medication withdrawal period or those with sustained supine hypertension ≥180/110mmHg. * Clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months. * Clinically significant pulmonary, renal, hematopoietic, hepatic disease, or 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Augmentation Index | 1 hour post-intervention tilt table test | Change from baseline in upright augmentation index, used as a marker of cardiovascular risk associated with systemic arterial stiffness, wave reflection, and the resulting pulsatile workload imposed on the left ventricle. Higher values suggest greater risk. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLuis Okamoto, MD
Vanderbilt University Medical Center
Participant flow
Recruitment details
31 subjects were enrolled and underwent screening procedures.
Pre-assignment details
Of the 31 subjects enrolled, 9 subjects did not complete the study
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 8 |
| Orthostatic drop in systolic blood pressure, mm Hg | -61 mm Hg STANDARD_DEVIATION 39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
None listed