Healthy Volunteers
Conditions
Keywords
Healthy
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).
Interventions
DRUGPlacebo
Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital
DRUGFludrocortisone
Fludrocortisone 0.1 mg
DRUGEplerenone
Epleronone 100 mg
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum aldosterone after angiotensin II infusion | 5 days | Aldosterone levels after 30 mins AngII infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum aldosterone after cosyntropin infusion | 5 days | Aldosterone levels after 30 mins cosyntropin infusion |
| Serum cortisol after angiotensin II infusion | 5 days | Cortisol levels after 30 mins AngII infusion |
| Serum cortisol after cosyntropin infusion | 5 days | Cortisol levels after 30 mins cosyntropin infusion |
Countries
United States
Outcome results
None listed