Sex Differences in the Dilatory Response of Compound 21

NCT ID: NCT05576155

Last Updated: 2024-12-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-03
• Study Completion Date: 2023-02-23

Brief 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.

Conditions

Sex Differences

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Local losartan perfusion

\~1 hour of losartan is perfused through an intradermal microdialysis fiber

Group Type: EXPERIMENTAL

Compound 21 + losartan

Intervention Type: DRUG

Compound 21 + losartan (43 µM) is perfused at 10 doses increasing serially for 10 minutes each from 10\^-12 M to 10\^-3 M.

Local lactated Ringer's (control) perfusion

\~1 hour of lactated Ringer's is perfused through an intradermal microdialysis fiber

Group Type: OTHER

Compound 21

Intervention Type: DRUG

Compound 21 + Ringer's is perfused at 10 doses increasing serially for 10 minutes each from 10\^-12 M to 10\^-3 M

Interventions

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Anna Stanhewicz, PhD

OTHER

Sponsor Role: lead

Responsible Party

Anna Stanhewicz, PhD

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anna Stanhewicz, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

202206519

Identifier Type: -

Identifier Source: org_study_id