The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production

NCT ID: NCT02871648

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2019-12-31

Brief Summary

The purpose of this research protocol is to determine if the same effects are observed in vivo in humans using a similar approach. Demonstrating that mineralocorticoid acts on zona glomerulosa cells to regulate aldosterone production in a short feedback loop would provide important insight into hormone regulation, and explain variability in pathophysiologic states such as hypertension and cardiovascular diseases.

Detailed Description

In order to provide additional evidence indicating the presence of functional and in order to provide additional evidence indicating the presence of functional mineralocorticoid receptors (MR) on zona glomerulosa (ZG) cells, the investigators propose the following protocol in healthy volunteers. The investigators will evaluate aldosterone and cortisol production in response to an angiotensin II infusion after three separate test conditions: 1) placebo, 2) following a single dose of fludrocortisone, and 3) following a single dose of eplerenone (a MR antagonist).

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital

Fludrocortisone

Subjects will receive 0.1 mg of fludrocortisone (Florinef) on one of three study days.

Group Type: ACTIVE_COMPARATOR

Fludrocortisone

Intervention Type: DRUG

Fludrocortisone 0.1 mg

Epleronone

Subjects will receive 100 mg of epleronone on one of three study days.

Group Type: ACTIVE_COMPARATOR

Eplerenone

Intervention Type: DRUG

Epleronone 100 mg

Interventions

Placebo

Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital

Intervention Type: DRUG

Fludrocortisone

Fludrocortisone 0.1 mg

Intervention Type: DRUG

Eplerenone

Epleronone 100 mg

Intervention Type: DRUG

Other Intervention Names

Florinef; Inspra

Eligibility Criteria

Inclusion Criteria

• Participants must be healthy, with no prior history of hypertension, no family history of hypertension, diabetes, stroke or cardiac disease in first-degree relatives before the age of 70 years and have an average (two measurements) blood pressure of <130/89 mm Hg and >100/50 mmHg at the screening visit.
• All subjects will have body mass index 19-25 kg/m2.
• Subjects must have normal laboratory values for: Complete blood count; serum creatinine, sodium, potassium, glucose, liver enzymes; urinalysis; negative urine HCG in women; normal ECG

Exclusion Criteria

• Alcohol intake >12oz per week, as well as tobacco or recreational drug use.
• Any subject with a history of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months will be excluded from the study.
• Subjects taking any prescription medications (with the exception of birth control pills) or herbal medications will be excluded.
• Because of the unknown risk of infused angiotensin II in pregnancy, women who are pregnant will be excluded from study and all women will be screened for pregnancy by quantitative serum hCG measurement on the day of each CCI admission.
• Women currently breastfeeding will also be excluded from the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gordon H. Williams, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan S Williams, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Braley LM, Williams GH. Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study. Am J Physiol. 1977 Nov;233(5):E402-6. doi: 10.1152/ajpendo.1977.233.5.E402.

Reference Type: BACKGROUND

PMID: 200147 (View on PubMed)

Other Identifiers

2015P001664

Identifier Type: -

Identifier Source: org_study_id