Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Sponsor

University of Missouri-Columbia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05219799

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity Vasodilation Healthy	Drug: Propranolol Hydrochloride Drug: Isoproterenol Drug: Acetylcholine Drug: Sodium Nitroprusside Drug: Norepinephrine	Early Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Hypoxia Exposure 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.	Drug: Propranolol Hydrochloride Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures Drug: Isoproterenol Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness Drug: Acetylcholine Dose response (2, 4, 8, and 16 mcg/dL/min) regional infusion to assess vasodilation Drug: Sodium Nitroprusside Dose response (0.5, 1, and 2 mcg/dL/min) regional infusion to assess vasodilation Drug: Norepinephrine Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

Arm

Intervention/Treatment

Other: Hypoxia Exposure

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.

Drug: Propranolol Hydrochloride

Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures

Drug: Isoproterenol

Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness

Drug: Acetylcholine

Dose response (2, 4, 8, and 16 mcg/dL/min) regional infusion to assess vasodilation

Drug: Sodium Nitroprusside

Dose response (0.5, 1, and 2 mcg/dL/min) regional infusion to assess vasodilation

Drug: Norepinephrine

Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

Outcome Measures

Primary Outcome Measures

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 Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy weight (BMI >18 and <25 kg/m2)
Obese (BMI ≥30 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Missouri	Columbia	Missouri	United States	65211

Sponsors and Collaborators

University of Missouri-Columbia

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jacqueline K Limberg, PhD, Assistant Professor, University of Missouri-Columbia

ClinicalTrials.gov Identifier:

NCT05219799

Other Study ID Numbers:

2080504

First Posted:

Feb 2, 2022

Last Update Posted:

Mar 25, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 25, 2022