Clinical trial NCT05146089: Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences
Official title: Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Sleep Apnea
Healthy
Vasoconstriction
Vasodilation
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Mayo Clinic
First posted: 2021-12-06
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Subjects will be asked to complete 1 1-hour screening visit, 1 overnight at-home monitoring, and 1 (women) or 2 (men) 5-hour study visits. Subjects will not be blinded to study condition and all subjects will serve as their own controls. All study visits will be separated by a minimum of 1 week and will occur at the same time of day.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Muscle sympathetic nerve activity (MSNA)
timeFrame: Change from baseline after hypoxia exposure
Secondary outcomes:
measure: Arterial blood pressure
timeFrame: Change from baseline after hypoxia exposure
Other outcomes:
Locations:
city: Columbia
country: United States
facility: University of Missouri-Columbia
state: Missouri
city: Rochester
country: United States
facility: Mayo Clinic
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Jacqueline K Limberg, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: