Sex Differences in the Dilatory Response of Compound 21

NCT05576155 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 202206519
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Circulating Progesterone and Testosterone

  at the start of the experimental visit, immediately prior to local losartan treatment

• Circulating Estradiol

  at the start of the experimental visit, immediately prior to local losartan treatment

Study Arms (2)

Local losartan perfusion

EXPERIMENTAL

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

Drug: Compound 21 + losartan

Local lactated Ringer's (control) perfusion

OTHER

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

Drug: Compound 21

Interventions

Compound 21 DRUG

Compound 21 + Ringer's 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

Compound 21 + losartan 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 losartan perfusion

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Young women or men,
• years old,
• Body mass index between 18 and 30 kg/m2,
• Systolic blood pressure \<140,
• Diastolic blood pressure \<90 mmHg.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Interventions

compound 21; Losartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Kelsey Schwartz
• Organization: University of Iowa

kelsey-schwartz@uiowa.edu

319-467-3096

Study Officials

• Anna Stanhewicz, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 12, 2022
• Study Start: October 3, 2022
• Primary Completion: February 23, 2023
• Study Completion: February 23, 2023
• Last Updated: December 31, 2024
• Results First Posted: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)