Healthy Subjects
Conditions
Brief summary
The purpose of this research protocol is to determine if the same effects are observed in vivo in humans through a randomized controlled study. Data regarding a novel mechanism of the widely used statin class of medications on the mineralocorticoid pathway would likely have significant clinical implications on the future management of hypertension and other cardiovascular disease given the known pleiotropy of aldosterone action.
Detailed description
In order to provide additional evidence regarding the effect of statin therapy on aldosterone levels, the investigators propose the following randomized, double-blinded, placebo controlled protocol in relatively healthy volunteers. The investigators will evaluate aldosterone and cortisol production in response to an angiotensin II infusion under the following test conditions: 1) placebo, 2) simvastatin therapy (lipophilic statin), and 3) pravastatin therapy (hydrophilic statin). Measurements will be made to assess the effect of both acute (single dose) and chronic (6 and 12 weeks) therapy of the two statin medications.
Interventions
DRUGSimvastatin
Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure
DRUGPravastatin
Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure
OTHERPlacebo
Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Blood pressure \<140/90 mmHg and \>90/50 mmHg * Body mass index 19-40 kg/m2 * Normal screening laboratory values for: i. Serum sodium, potassium, glucose, liver enzymes ii. GFR (\>60 mL/min/1.73m2) iii. A1c iv. TSH * Normal ECG * Negative urine HCG at screening for women who are able to become pregnant.
Exclusion criteria
* Any prior use of statin therapy * History of coronary disease, diabetes, hypertension, stroke, kidney disease, thyroid disease, psychiatric illness, malignancy, preeclampsia, or illness requiring overnight hospitalization in the past 6 months * Triglycerides \> 500, LDL \> 200 * Any prescription medication or herbal medication including oral contraceptive, excluding thyroid medications * Unstable thyroid disease (determined by abnormal TSH) * Pregnancy or current breastfeeding * Alcohol intake \>12 oz per week * Tobacco or recreational drug use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum aldosterone following angiotensin II infusion | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| 24 hour urine aldosterone | Baseline |
Countries
United States
Outcome results
None listed