The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production

Healthy Volunteers Clinical Trial

Official title:

The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02871648
• Other study ID #: 2015P001664
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: December 2019

Study information

• Verified date: June 2021
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Placebo
Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital
• Fludrocortisone
Fludrocortisone 0.1 mg
• Eplerenone
Epleronone 100 mg

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum aldosterone after angiotensin II infusion	Aldosterone levels after 30 mins AngII infusion	5 days
Secondary	Serum aldosterone after cosyntropin infusion	Aldosterone levels after 30 mins cosyntropin infusion	5 days
Secondary	Serum cortisol after angiotensin II infusion	Cortisol levels after 30 mins AngII infusion	5 days
Secondary	Serum cortisol after cosyntropin infusion	Cortisol levels after 30 mins cosyntropin infusion	5 days