Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity

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 Overview

• Status: Recruiting
• Conditions: Healthy; Obesity; Vasodilation; Vasoconstriction
• Intervention / Treatment: Other: Hypoxia Exposure; Drug: Phenylephrine; Drug: Dexmedetomidine; Drug: Phentolamine; Drug: Norepinephrine

• Study Type: Interventional
• Enrollment (Anticipated): 104
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jennifer L Harper, B.S.; Phone Number: 573-882-2544; Email: harperjl@missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Recruiting
      • University of Missouri-Columbia
      • Contact: Jacqueline K Limberg, Ph.D.; Phone Number: 573-882-2420; Email: limbergj@Missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-45 years of age (premenopausal)
• Healthy weight (BMI ≥18 and ≤25 kg/m2)
• Obese (BMI ≥30 kg/m2)

Exclusion Criteria:

• Pregnancy, breastfeeding, oral hormonal contraceptive use
• Diagnosed sleep apnea or Oxygen desaturation index >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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypoxia Exposure; A physician will place a catheter in the brachial artery for intra-arterial pharmacological infusions. The following drugs will be administered to each participant under room air (normoxic) and low oxygen (hypoxic) conditions: phenylephrine, dexmedetomidine, norepinephrine, phentolamine (see Interventions for details).

Other: Hypoxia Exposure; Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.; Drug: Phenylephrine; Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.; Other Names: Phenylephrine Hydrochloride; Drug: Dexmedetomidine; Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.; Drug: Phentolamine; Phentolamine will be locally infused via brachial artery catheter for 10 min before baseline measurement (12 mcg/dL/min) and the infusion will continue at a maintenance rate (5 mcg/dL/min) during acute normoxia and hypoxia.; Other Names: Phentolamine mesylate; Drug: Norepinephrine; Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in forearm vascular conductance with intra-arterial drug infusion	Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.	Continuous measurement of vascular conductance during infusion of each drug (final 3 min of normoxia and hypoxia).

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Protective Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Hypnotics and Sedatives; Respiratory System Agents; Sympathomimetics; Adrenergic alpha-Antagonists; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Dexmedetomidine; Norepinephrine; Phenylephrine; Oxymetazoline; Phentolamine
• Other Study ID Numbers: 2022525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No