Sex Differences in the Dilatory Response of Compound 21

Sex Differences Clinical Trial

Official title:

Sex Differences in the Dilatory Response of Compound 21

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05576155
• Other study ID #: 202206519
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: October 3, 2022
• Est. completion date: October 1, 2023

Study information

• Verified date: September 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

When blood pressure changes, Angiotensin II is produced and released into the bloodstream. This substance can make blood vessels smaller (i.e., vasoconstriction) by acting through Angiotensin II type I receptors (AT1R) to increase blood pressure. Or it can increase the diameter of vessels (i.e., vasodilation) through Angiotensin II type II receptors (AT2R) to decrease blood pressure. These two receptors normally work in balance to maintain blood pressure. However, excess Angiotensin II released in the bloodstream may reduce the sensitivity of AT2Rs, leading to excessive activation of AT1Rs. This results in increased constriction which plays a major role in diseases such as high blood pressure, hardening of the arteries, and heart failure. In the body, Angiotensin II production is reduced in the presence of estrogen, as seen in pre-menopausal women. Pre-menopausal women have a greater protection against cardiovascular diseases compared to age-matched males, likely due to the protective effects of estrogen. However, the extent that estrogen may impact the sensitivity of Angiotensin II receptors in pre-menopausal is unknown.

In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents), the blood vessels in a dime-sized area of the skin are studied in healthy young women and men. As a compliment to these measurements, blood is drawn from the subjects and circulating factors that may contribute to cardiovascular health are measured.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: October 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Young women or men,

• 18-35 years old,

• Body mass index between 18 and 30 kg/m2,

• Systolic blood pressure <140,

• Diastolic blood pressure <90 mmHg.

Exclusion Criteria:

• Skin allergies, skin disorders, or skin diseases such as Raynaud's phenomenon or other history of cold intolerance,

• History of metabolic or cardiovascular disease,

• Taking medications that could alter vascular function, including antidepressants, anxiety medications, or cholesterol or blood pressure lowering drugs,

• Women with oligo- or amenorrhea,

• Women that are pregnant or nursing

• current tobacco use,

• Allergy to materials used during the experiment (e.g. latex).

Related Conditions & MeSH terms

• Sex Differences

Intervention

Drug:
• Compound 21
Compound 21 + Ringer's is perfused at 10 doses increasing serially for 10 minutes each from 10^-12 M to 10^-3 M
• Compound 21 + losartan
Compound 21 + losartan (43 µM) is perfused at 10 doses increasing serially for 10 minutes each from 10^-12 M to 10^-3 M.

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Anna Stanhewicz, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microvascular AT2R sensitivity following local control treatment	cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 in young men and women	post 1 hour of local control treatment
Primary	Microvascular AT2R sensitivity following local AT1R inhibition	cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 co-infused with losartan young men and women	post 1 hour of local losartan treatment
Secondary	circulating hormones	plasma measurement of circulating estradiol, progesterone, and testosterone; measured by ELISA in plasma samples	a total of 1 time during the experiment