Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

University of Missouri (MU)

Status and phase: Completed; Early Phase 1

Conditions: Healthy; Vasodilation; Sleep Apnea; Vasoconstriction

Treatments: Drug: Oral Bosentan 62.5 mg; Other: modified Oxford test; Other: Hypoxic ventilatory response test; Other: Hypoxic exposure

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05146089

R00HL130339 (U.S. NIH Grant/Contract)

2007973

K99HL130339 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

Hypoxia Exposure

Experimental group

Description:

Men and women will be exposed to acute intermittent hypoxic episodes.

Treatment:

Other: Hypoxic exposure

Other: Hypoxic ventilatory response test

Drug: Oral Bosentan 62.5 mg

Other: modified Oxford test