Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

NCT05219799 — Early Phase 1, Recruiting, 72 participants, University of Missouri-Columbia

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Registry	NCT05219799
Status	Recruiting
Phase	Early Phase 1
Study type	Interventional; na, single group, masking: none, basic science
Enrollment	72 (Estimated)
Sponsor	University of Missouri-Columbia (Other)
Conditions	Obesity, Vasodilation, Healthy
Interventions	Propranolol Hydrochloride, Isoproterenol, Phentolamine Mesylate, Norepinephrine (Drug)
Dates	start 2023-03-14, primary completion 2027-07-30 (estimated), completion 2027-07-30 (estimated), first posted 2022-02-02, last updated 2026-07-28
Locations	1 site in United States

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
Hypoxia Exposure	Other	Drug: Propranolol Hydrochloride; Drug: Isoproterenol; Drug: Phentolamine Mesylate; Drug: 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.

Propranolol Hydrochloride (Drug): Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures
Isoproterenol (Drug): Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness
Phentolamine Mesylate (Drug): This infusion will be for 10 min before baseline measurement (12 mcg/dL/min) and continue the infusion at a maintenance rate (5 mcg/dL/min).
Norepinephrine (Drug): Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

+Outcome measures

Primary outcomes

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.

+Eligibility

Sex: All, ages: 18 Years to 45 Years, accepts healthy volunteers

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

+Locations (1)

Facility	City	Country	Status
University of Missouri	Columbia, Missouri	United States	Recruiting

+Investigators

Jacqueline Limberg, Ph.D., Principal investigator, University of Missouri-Columbia