Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

Healthy Clinical Trial

Official title:

Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05146089
• Other study ID #: 2007973
• Secondary ID: K99HL130339R00HL
• Status: Completed
• Phase: Early Phase 1
• Start date: December 20, 2016
• Est. completion date: April 12, 2021

Study information

• Verified date: November 2021
• Source: University of Missouri-Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: April 12, 2021
• Est. primary completion date: September 8, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Hypoxia
• Sleep Apnea
• Vasoconstriction
• Vasodilation

Intervention

Other:
• Hypoxic exposure
30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.
• modified Oxford test
An intravenous bolus of sodium nitroprusside (100 µg) will be given to decrease blood pressure, followed 1 minute later by a bolus of phenylephrine (150 µg) to increase blood pressure, occurring before and after intermittent hypoxia exposure.

Drug:
• Oral Bosentan 62.5 mg
Prior to completion of visit 2, male subjects will consume 62.5 mg twice daily for 3 days as well as the morning of the study visit (7 pills) at home and experimental sessions will be performed 3 hours after oral intake of the final dose.

Other:
• Hypoxic ventilatory response test
Hypoxia will be achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask. This will be repeated 4-5 times per test, occurring before and after intermittent hypoxia exposure.

Locations

Country	Name	City	State
United States	University of Missouri-Columbia	Columbia	Missouri
United States	Mayo Clinic	Rochester	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
University of Missouri-Columbia	Mayo Clinic, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle sympathetic nerve activity (MSNA)	MSNA burst incidence (bursts/100 heart beats)	Change from baseline after hypoxia exposure
Secondary	Arterial blood pressure	Systolic blood pressure, Diastolic blood pressure, Mean blood pressure	Change from baseline after hypoxia exposure