Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Early Phase 1

Recruiting

• Conditions: Obesity; Vasodilation; Healthy
• Interventions: Drug: Propranolol Hydrochloride; Drug: Isoproterenol; Drug: Phentolamine Mesylate; Drug: Norepinephrine

• Registration Number: NCT05219799
• Lead Sponsor: University of Missouri-Columbia

Brief Summary

The purpose of this project is to examine key mechanisms contributing to sex-differences in hypoxic vasodilation and the impact of obesity, with particular emphasis on the sympathetic nervous system.

Detailed Description

Patients with sleep apnea are at increased risk of developing cardiovascular disease - with women at potentially greater risk than men. Contributing mechanisms are not well understood, but may be related to how women respond to low oxygen and, given over 70% of patients with sleep apnea are obese, the impact of obesity. This project seeks to increase our understanding of mechanisms that may contribute to sex differences in the cardiovascular response to low oxygen with the hope that this knowledge will improve the efficacy of current therapies and support the discovery of novel therapeutics.

Study Timeline

• Study First Submitted: 2022-01-21
• Study First Submitted QC: 2022-01-21
• Study First Posted: 2022-02-02
• Study Start: 2023-03-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-28
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• BMI >18 kg/m2

Exclusion Criteria

• Pregnancy, breastfeeding
• Diagnosed sleep apnea or AHI >10 events/hr
• Current smoking/Nicotine use
• Increased risk of bleeding, pro-coagulant disorders, clotting disorders, anticoagulation therapy
• Nerve/neurologic disease
• Cardiovascular, hepatic, renal, respiratory disease
• Blood pressure ≥140/90 mmHg
• Diabetes, Polycystic ovarian syndrome
• Communication barriers
• Prescription medications, Sensitivity to lidocaine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypoxia Exposure	Propranolol Hydrochloride	Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.
Hypoxia Exposure	Phentolamine Mesylate	Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.
Hypoxia Exposure	Norepinephrine	Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.
Hypoxia Exposure	Isoproterenol	Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.

Primary Outcome Measures

Name	Time	Method
Change in forearm vascular conductance with intra-arterial drug infusion	Change from baseline to last 1-minute of drug infusion	Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.

Trial Locations

Locations (1)

University of Missouri; 🇺🇸 Columbia, Missouri, United States