The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production

Mass General Brigham

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: Fludrocortisone; Drug: Eplerenone

Study type: Interventional

Funder types: Other

Identifiers

NCT02871648

2015P001664

Details and patient eligibility

About

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.

Full 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).

Enrollment: 23 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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23 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Fludrocortisone

Active Comparator group

Description:

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

Treatment:

Drug: Fludrocortisone

Epleronone

Active Comparator group

Description:

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

Treatment:

Drug: Eplerenone