Sex Differences in the Dilatory Response of Compound 21

• Sponsor: Anna Stanhewicz, PhD (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05576155
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 11.9
• Patients Per Site Per Month: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sex Differences	Drug: Compound 21; Drug: Compound 21 + losartan	Early Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Sex Differences in the Dilatory Response of Compound 21
• Actual Study Start Date: Oct 3, 2022
• Anticipated Primary Completion Date: Apr 1, 2023
• Anticipated Study Completion Date: Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Local losartan perfusion ~1 hour of losartan is perfused through an intradermal microdialysis fiber	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.
Other: Local lactated Ringer's (control) perfusion ~1 hour of lactated Ringer's is perfused through an intradermal microdialysis fiber	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

Outcome Measures

Primary Outcome Measures

1. Microvascular AT2R sensitivity following local control treatment [post 1 hour of 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

2. Microvascular AT2R sensitivity following local AT1R inhibition [post 1 hour of local losartan treatment]

   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

Secondary Outcome Measures

1. circulating hormones [a total of 1 time during the experiment]

   plasma measurement of circulating estradiol, progesterone, and testosterone; measured by ELISA in plasma samples

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

• Anna Stanhewicz, PhD

Investigators

• Principal Investigator: Anna Stanhewicz, PhD, University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anna Stanhewicz, PhD, Assistant Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT05576155
• Other Study ID Numbers: 202206519
• First Posted: Oct 12, 2022
• Last Update Posted: Oct 18, 2022
• Last Verified: Oct 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Compound 21; Losartan

Study Results

No Results Posted as of Oct 18, 2022