Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

NCT ID: NCT05146089

Last Updated: 2021-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-20

Study Completion Date

2021-04-12

Brief Summary

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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

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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.

Conditions

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Sleep Apnea Healthy Vasoconstriction Vasodilation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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 Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Hypoxia Exposure

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

Group Type EXPERIMENTAL

Hypoxic exposure

Intervention Type OTHER

30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.

modified Oxford test

Intervention Type OTHER

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.

Oral Bosentan 62.5 mg

Intervention Type DRUG

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.

Hypoxic ventilatory response test

Intervention Type OTHER

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.

Interventions

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Hypoxic exposure

30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.

Intervention Type OTHER

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.

Intervention Type OTHER

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.

Intervention Type DRUG

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.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

University of Missouri-Columbia

OTHER

Sponsor Role lead

Responsible Party

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Jacqueline K Limberg, PhD

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jacqueline K Limberg, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

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University of Missouri-Columbia

Columbia, Missouri, United States

Site Status

Mayo Clinic

Rochester, Missouri, United States

Site Status

Countries

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United States

Other Identifiers

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K99HL130339

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R00HL130339

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007973

Identifier Type: -

Identifier Source: org_study_id