Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
Primary Purpose
Obesity, Vasodilation, Healthy
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Propranolol Hydrochloride
Isoproterenol
Phentolamine Mesylate
Norepinephrine
Sponsored by
About this trial
This is an interventional basic science trial for Obesity
Eligibility Criteria
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
Sites / Locations
- University of MissouriRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Hypoxia Exposure
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT05219799
First Posted
January 21, 2022
Last Updated
April 3, 2023
Sponsor
University of Missouri-Columbia
1. Study Identification
Unique Protocol Identification Number
NCT05219799
Brief Title
Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
Official Title
Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2023 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Missouri-Columbia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Vasodilation, Healthy
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hypoxia Exposure
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Propranolol Hydrochloride
Intervention Description
Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures
Intervention Type
Drug
Intervention Name(s)
Isoproterenol
Intervention Description
Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness
Intervention Type
Drug
Intervention Name(s)
Phentolamine Mesylate
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Norepinephrine
Intervention Description
Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures
Primary Outcome Measure Information:
Title
Change in forearm vascular conductance with intra-arterial drug infusion
Description
Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.
Time Frame
Change from baseline to last 1-minute of drug infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer L Harper, B.S.
Phone
5738822544
Email
harperjl@missouri.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacqueline Limberg, Ph.D.
Organizational Affiliation
University of Missouri-Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Missouri
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65211
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer L Harper
Phone
573-882-2544
Email
harperjl@missouri.edu
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
We'll reach out to this number within 24 hrs