Overnight Trials With Heat Stress in Autonomic Failure Patients With Supine Hypertension

Overnight Trials to Compare the Effects of Controlled Heat Stress Versus Sham Control on Nocturnal Supine Hypertension in Autonomic Failure Patients

Patients with autonomic failure are characterized by disabling orthostatic hypotension (low blood pressure on standing), and at least half of them also have high blood pressure while lying down (supine hypertension). Exposure to heat, such as in hot environments, often worsens their orthostatic hypotension. The causes of this are not fully understood. The purpose of this study is to evaluate whether applying local heat over the abdomen of patients with autonomic failure and supine hypertension during the night would decrease their nocturnal high blood pressure while lying down. This will help us better understand the mechanisms underlying this phenomenon, and may be of use in the treatment of supine hypertension.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Multiple System Atrophy; Pure Autonomic Failure; Autonomic Failure
• Intervention / Treatment: Other: Heating pad; Other: Sham control

Detailed Description

Primary autonomic failure is a neurodegenerative condition characterized by loss of efferent sympathetic function and severe baroreflex impairment. The clinical hallmark of autonomic failure is disabling orthostatic hypotension, but at least half of patients are also hypertensive while lying down. This supine hypertension can be severe and associated with end-organ damage and worsening of orthostatic hypotension due to increased pressure natriuresis. It also complicates the management of these patients by limiting the use of daytime pressor agents for the treatment of orthostatic hypotension. Currently, no antihypertensive drug effectively lowers BP and prevents pressure natriuresis without worsening standing BP.

It is well known that heat exposure (e.g. hot weather or a hot bath or shower) produces an acute and temporary worsening of orthostatic hypotension in autonomic failure patients. Factors that may predispose these patients to the lowering BP effects of heat stress include 1) impaired heat dissipation due to inability to sweat, 2) preserved heat-mediated skin vasodilation, and 3) blunted sympathetic hemodynamic responses to maintain BP (increases in cardiac output, heart rate, and vaso- and venoconstriction). Our preliminary results showed that 2 hours of passive heat stress lowers BP in these patients through a decrease in central volume. In this study, we will assess the efficacy and safety of passive heat stress in the treatment of nocturnal supine hypertension in autonomic failure patients. Our hypothesis is that controlled local (abdominal) passive heat stress applied during the night will lower nocturnal BP in autonomic failure patients with supine hypertension.

To test this hypothesis, we propose to compare the BP effects of passive heat applied during the night vs. a sham control in a randomized crossover study in autonomic failure patients with supine hypertension.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bonnie K Black, RN; Phone Number: 615-343-6862; Email: autonomics@vumc.org
• Study Contact Backup: Name: Italo Biaggioni, MD; Email: autonomics@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Autonomic Dysfunction Center/ Vanderbilt University Medical Center
      • Sub-Investigator: David Robertson, MD
      • Sub-Investigator: jorge Celedonio, MD
      • Contact: Emily C Smith, RN; Phone Number: 615-875-1516; Email: autonomics@vumc.org
      • Contact: Bonnie K Black, RN; Phone Number: 615-322-3304; Email: autonomics@vumc.org
      • Sub-Investigator: Bonnie K Black, RN
      • Sub-Investigator: Luis E Okamoto, MD
      • Principal Investigator: Italo Biaggioni, MD
      • Sub-Investigator: Alfredo Gamboa, MD
      • Sub-Investigator: Cyndya A Shibao, MD
      • Sub-Investigator: Andre Diedrich, MD, PhD
      • Sub-Investigator: Emily C Smith, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients, between 18-80 yrs., with primary autonomic failure (Parkinson Disease, Multiple System Atrophy, and Pure Autonomic Failure) and supine hypertension. Supine hypertension will be defined as SBP≥150 mmHg.
• Patients able and willing to provide informed consent.

Exclusion Criteria:

• Pregnancy
• Significant cardiac, renal or hepatic illness, or with contraindications to administration of pressor agents or with 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Heat Stress; Passive heat-stress using a commercial heating pad applied on the trunk	Other: Heating pad; Heat stress applied on the trunk for up to 8 hours; Other Names: Local heat stress
Sham Comparator: Control (Non-heating); Commercial heating pad applied on the trunk but turned off	Other: Sham control; heating pad turned off applied on the trunk for up to 8 hours; Other Names: control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	Maximal change from baseline in systolic blood pressure during the night, measured from 10 pm to 8 am	10 pm - 8 am

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Orthostatic Tolerance the following morning	Orthostatic tolerance defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test	10 min standing

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Italo Biaggioni, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Okamoto LE, Celedonio JE, Smith EC, Gamboa A, Shibao CA, Diedrich A, Paranjape SY, Black BK, Muldowney JAS 3rd, Peltier AC, Habermann R, Crandall CG, Biaggioni I. Local Passive Heat for the Treatment of Hypertension in Autonomic Failure. J Am Heart Assoc. 2021 Apr 6;10(7):e018979. doi: 10.1161/JAHA.120.018979. Epub 2021 Mar 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2017
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimated): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: orthostatic hypotension; autonomic failure; heat stress; supine hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Hypertension; Multiple System Atrophy; Shy-Drager Syndrome; Pure Autonomic Failure; Heat Stress Disorders
• Other Study ID Numbers: VR22699; 141523 (Other Identifier: Vanderbilt IRB)

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: No
• product manufactured in and exported from the U.S.: No