CPAP for the Treatment of Supine Hypertension

Hemodynamic Effects of Positive Airway Pressure to Treat Supine Hypertension and Improve Neurogenic Orthostatic Hypotension

This study aims to learn about the effects of continuous positive airway pressure (CPAP) on people with autonomic failure and high blood pressure when lying down (supine hypertension) to determine if it can be used to treat their high blood pressure during the night. CPAP (a widely used treatment for sleep apnea) involves using a machine that blows air into a tube connected to a mask covering the nose, or nose and mouth, to apply a low air pressure in the airways.

The study includes 3-5 days spent in the Vanderbilt Clinical Research Center (CRC): at least one day of screening tests, followed by up to 3 study days. Subjects may be able to participate in daytime and/or overnight studies. The Daytime study consists of 2 study days: one with active CPAP and one with sham CPAP applied for up to 2 hours. The Overnight study consists of 3 study nights: one with active CPAP, one with sham CPAP, both applied for up to 9 hours and one night sleeping with the bed tilted head-up.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; Neurogenic Orthostatic Hypotension; Pure Autonomic Failure; Supine Hypertension; Autonomic Failure
• Intervention / Treatment: Device: Active CPAP; Device: Sham CPAP; Other: Sleeping in a head-up tilt (HUT) position

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 and/or 2 study nights.

Screening tests include a physical examination and history, routine safety laboratory assessments, and autonomic nervous system testing. Medications for high blood pressure will be held for at least 5 half-lives before studies. Subjects may be able to participate in the daytime and/or the overnight studies.

Daytime Study:

Eligible participants will be studied on two separate days in random order: one day with a high CPAP level and one day with a low CPAP level. The active CPAP level will be determined during a CPAP titration trial

On each study day, participants will be instrumented to measure blood pressure, heart rate, hemodynamic parameters, segmental impedance, and markers of cardiovascular risk. A saline lock or IV catheter will be inserted in one of the arm's veins for blood sample collection. Urine will also be collected during studies.

After baseline measurements, active or sham CPAP will then be applied for up to 2 hours. Outcome measurements will be repeated after 1 and 2 hours of CPAP.

Overnight Studies:

Eligible participants will be studied on three separate nights in random order with a active CPAP, sham CPAP, and sleeping in a head-up tilt position. The active CPAP level will be determined during a CPAP titration trial.

On each study night, the intervention (active CPAP, sham CPAP, or head-up tilt position) will be applied for up to 9 hours. Blood pressure, heart rate, hemodynamic parameters, and markers of cardiovascular risk will be assessed throughout the night. Urine will also be collected during this period. On the following morning, participants will have a tilt table test.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bonnie K Black, RN, NP; Phone Number: 615-343-6862; Email: bonnie.black@vumc.org
• Study Contact Backup: Name: Luis E Okamoto, MD; Phone Number: 615-936-6119; Email: luis.e.okamoto@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Autonomic Dysfunction Center/ Vanderbilt University Medical Center
      • Principal Investigator: Italo Biaggioni, MD
      • Sub-Investigator: Alfredo Gamboa, MD
      • Sub-Investigator: Cyndya A Shibao, MD
      • Sub-Investigator: Andre Diedrich, MD, PhD
      • Contact: Bonnie K Black, RN, NP; Phone Number: 615-343-6862; Email: bonnie.black@vumc.org
      • Contact: Luis E Okamoto, MD; Phone Number: (615) 936-6119; Email: luis.e.okamoto@vumc.org
      • Principal Investigator: Luis E Okamoto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
• Nocturnal supine hypertension (nighttime systolic blood pressure ≥140 mmHg) during the overnight screening for supine hypertension.
• Patients who are willing and able to provide informed consent

Exclusion Criteria:

• Patients with history of recent facial trauma or surgery or intolerance to CPAP or to the CPAP mask.
• Patients who cannot tolerate the medication withdrawal, defined as those who are unable to stand for at least one minute or those with sustained supine blood pressure ≥180/110 mmHg after the medication withdrawal period.
• Bedridden patients or those who are unable to stand due to motor impairment or severe orthostatic hypotension.
• Smokers, patients who are pregnant, or have clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months; heart failure; and other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical or laboratory testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active CPAP (Daytime Study); CPAP at 8, 10, or 12 cm H2O is applied for up to 2 hours while supine and awake.	Device: Active CPAP; Continuous positive airway pressure (CPAP) is applied at 8, 10, or 12 cm H20. The active CPAP level will be determined during a CPAP titration trial; Other Names: Active continuous positive airway pressure
Sham Comparator: Sham CPAP (Daytime Study); Sham CPAP is applied for up to 2 hours while supine and awake.	Device: Sham CPAP; Sham continuous positive airway pressure applied at <4 cm H2O; Other Names: Sham continuous positive airway pressure
Experimental: Active CPAP (Overnight Study); CPAP at 8, 10, or 12 cm H2O is applied for up to 9 hours during the night.	Device: Active CPAP; Continuous positive airway pressure (CPAP) is applied at 8, 10, or 12 cm H20. The active CPAP level will be determined during a CPAP titration trial; Other Names: Active continuous positive airway pressure
Sham Comparator: Sham CPAP (Overnight Study); Sham CPAP is applied for up to 9 hours during the night.	Device: Sham CPAP; Sham continuous positive airway pressure applied at <4 cm H2O; Other Names: Sham continuous positive airway pressure
Active Comparator: Sleeping in a head-up tilt position (Overnight Study); Sleeping with the bed tilted head-up by 10 degrees for up to 9 hours during the night.	Other: Sleeping in a head-up tilt (HUT) position; Sleeping with the whole bed tilted head-up by 10 degrees or with the head elevated by 13-14 inches.; Other Names: HUT sleeping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure (daytime)	Change from baseline in systolic blood pressure at 2 hours of the intervention	day 1 and 2 (within 2 hours of the intervention)
Systolic blood pressure (overnight)	Area under the curve of the change from baseline in systolic blood pressure	up to 9 hours during the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke Volume (daytime)	Change from baseline in stroke volume at 1and 2 hours of the intervention	day 1 and 2 (within 2 hours of the intervention)
Natriuretic hormone (daytime)	Percent change from baseline in N-terminal-proatrial natriuretic peptide at 2 hours after the intervention	day 1 and 2 (within 2 hours of the intervention)
Nocturnal diuresis (overnight)	Urine volume collected during the night	up to 9 hours during the intervention
Morning orthostatic tolerance (overnight)	Area under the curve of the upright systolic blood pressure during head-up tilt	during 10 minutes upright tilt

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Italo Biaggioni, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: August 3, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; CPAP; Orthostatic hypotension
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Hypertension; Parkinson Disease; Multiple System Atrophy; Hypotension, Orthostatic; Pure Autonomic Failure; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Nervous System Physiological Phenomena; Sleep; Patient Positioning
• Other Study ID Numbers: 220821; 200124 (Other Identifier: VUMC IRB); R01HL161095 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No