Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity

NCT04436731 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2022525
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Healthy; Vasoconstriction; Vasodilation

Outcome Measures

Primary Outcomes (1)

• 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).

Study Arms (1)

Hypoxia Exposure

EXPERIMENTAL

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; Drug: Phenylephrine; Drug: Dexmedetomidine; Drug: Phentolamine; Drug: Norepinephrine

Interventions

Hypoxia Exposure OTHER

Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.

Hypoxia Exposure

Phenylephrine DRUG

Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.

Also known as: Phenylephrine Hydrochloride

Hypoxia Exposure

Dexmedetomidine DRUG

Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.

Hypoxia Exposure

Phentolamine DRUG

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.

Also known as: Phentolamine mesylate

Hypoxia Exposure

Norepinephrine DRUG

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

Hypoxia Exposure

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri-Columbia

Columbia, Missouri, 65211, United States

Location

MeSH Terms

Conditions

Obesity; Aneurysm

Interventions

Phenylephrine; Dexmedetomidine; Phentolamine; Norepinephrine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

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

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 18, 2020
• Study Start: December 9, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)