Sex Differences in the Dilatory Response of Compound 21

December 19, 2024 updated by: Anna Stanhewicz, PhD

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Microvascular AT2R Sensitivity Following Local Control Treatment
Time Frame: 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
post 1 hour of local control treatment
Microvascular AT2R Sensitivity Following Local AT1R Inhibition
Time Frame: 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
post 1 hour of local losartan treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Circulating Progesterone and Testosterone
Time Frame: at the start of the experimental visit, immediately prior to local losartan treatment
plasma measurement of circulating progesterone and testosterone; measured by ELISA in plasma samples
at the start of the experimental visit, immediately prior to local losartan treatment
Circulating Estradiol
Time Frame: at the start of the experimental visit, immediately prior to local losartan treatment
plasma measurement of circulating estradiol, measured by ELISA in plasma samples
at the start of the experimental visit, immediately prior to local losartan treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Anna Stanhewicz, PhD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anna Stanhewicz, PhD, University of Iowa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 3, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202206519

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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