Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

NCT05146089 | Completed Early Phase 1 FDA Drug

• 3 other identifiers: 2007973K99HL130339R00HL130339
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

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.

Conditions

Sleep Apnea; Healthy; Vasoconstriction; Vasodilation

Outcome Measures

Primary Outcomes (1)

• Muscle sympathetic nerve activity (MSNA)

  MSNA burst incidence (bursts/100 heart beats)

  Change from baseline after hypoxia exposure

Secondary Outcomes (1)

• Arterial blood pressure

  Change from baseline after hypoxia exposure

Study Arms (1)

Hypoxia Exposure

EXPERIMENTAL

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

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

Interventions

Hypoxic exposure OTHER

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

Hypoxia Exposure

modified Oxford test 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.

Hypoxia Exposure

Oral Bosentan 62.5 mg 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.

Hypoxia Exposure

Hypoxic ventilatory response test 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.

Hypoxia Exposure

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Missouri-Columbia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Mayo Clinic: collaborator

Study Sites (2)

University of Missouri-Columbia

Columbia, Missouri, 65211, United States

Location

Mayo Clinic

Rochester, Missouri, 55902, United States

Location

MeSH Terms

Conditions

Sleep Apnea Syndromes; Aneurysm

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jacqueline K Limberg, Ph.D.

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: December 6, 2021
• Study Start: December 20, 2016
• Primary Completion: September 8, 2018
• Study Completion: April 12, 2021
• Last Updated: December 6, 2021

Record last verified: 2021-11

Locations

US (2)