Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

Early Phase 1

Completed

• Conditions: Vasodilation; Healthy; Sleep Apnea; Vasoconstriction
• Interventions: Other: Hypoxic exposure; Other: modified Oxford test; Drug: Oral Bosentan 62.5 mg; Other: Hypoxic ventilatory response test

• Registration Number: NCT05146089
• Lead Sponsor: University of Missouri-Columbia

Brief Summary

The overall goal of this project is to better understand the effect of intermittent hypoxia (IH) on sympathetic neuronal discharge patterns in humans, as well as mechanisms that mediate persistent sympathoexcitation with IH.

Detailed Description

Sleep apnea is the most common form of sleep disordered breathing and patients with sleep apnea exhibit persistent activation of the sympathetic nervous system. Sympathoexcitation is also the final common pathway for a host of complications in conditions like obesity, hypertension, sleep apnea, and heart failure and plays a significant role in predicting negative clinical outcomes and deteriorating cardiovascular health. However, the mechanisms of sympathoexcitation with sleep apnea are poorly understood and thus make effective therapeutic approaches difficult to develop.

Intermittent hypoxia (IH) has been implicated in animal models as the primary stimulus for evoking increases in sympathetic activity with recurrent apneas. Thus, the overall goal of this application is to better understand the effect of IH on sympathetic discharge patterns in humans as well as the mechanisms mediating persistent sympathoexcitation with IH. By better understanding the effect of IH on sympathoexcitation, targeted therapeutic approaches might be devised to mitigate the effects of sympathetic over-activity on the cardiovascular system in conditions such as sleep apnea.

Study Timeline

• Study Start: 2016-12-20
• Primary Completion: 2018-09-08
• Study Completion: 2021-04-12
• Status Verified: 2021-11
• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-23
• Last Update Submitted: 2021-11-23
• Study First Posted: 2021-12-06
• Last Update Posted: 2021-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• healthy adult men and women;
• 18-45 years of age;
• BMI <30 kg/m2;
• non-pregnant/non-breastfeeding;
• non-smokers.

Exclusion Criteria

Subjects will be excluded if they are:

• taking any medications known to affect the cardiovascular or autonomic nervous system (e.g. alpha-blockers, beta-blockers, etc);
• Apnea Hypopnea Index >10 events/hr

Self-reported history of:

• hepatic, renal, pulmonary, cardiovascular, or neurological disease;
• stroke or neurovascular disease;
• bleeding/clotting disorders;
• sleep apnea or other sleep disorders;
• diabetes;
• smoking;
• history of alcoholism or substance abuse;
• hypertension.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypoxia Exposure	Hypoxic exposure	Men and women will be exposed to acute intermittent hypoxic episodes.
Hypoxia Exposure	modified Oxford test	Men and women will be exposed to acute intermittent hypoxic episodes.
Hypoxia Exposure	Hypoxic ventilatory response test	Men and women will be exposed to acute intermittent hypoxic episodes.
Hypoxia Exposure	Oral Bosentan 62.5 mg	Men and women will be exposed to acute intermittent hypoxic episodes.

Primary Outcome Measures

Name	Time	Method
Muscle sympathetic nerve activity (MSNA)	Change from baseline after hypoxia exposure	MSNA burst incidence (bursts/100 heart beats)

Secondary Outcome Measures

Name	Time	Method
Arterial blood pressure	Change from baseline after hypoxia exposure	Systolic blood pressure, Diastolic blood pressure, Mean blood pressure

Trial Locations

Locations (2)

Mayo Clinic; 🇺🇸 Rochester, Missouri, United States

University of Missouri-Columbia; 🇺🇸 Columbia, Missouri, United States