Effect of Statin Use on Aldosterone Secretion

Study Overview
=================
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.

Official Title
-----------------
Effect of Statin Use on Aldosterone Secretion

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: Simvastatin
* Drug: Pravastatin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital | Other: Placebo<br>* Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital<br>|
| Active Comparator: Simvastatin<br>Subjects in the simvastatin arm will receive simvastatin 20 mg daily for 6 weeks before having their lipids checked. If their LDL-c decreases by less than 35% from screening, then the dose of simvastatin is increased to 40 mg daily for the following 6 weeks. | Drug: Simvastatin<br>* Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure<br>* Other names: Zocor;|
| Active Comparator: Pravastatin<br>Subjects in the pravastatin arm will receive pravastatin 40 mg daily for 6 weeks before having their lipids checked. If their LDL-c decreases by less than 35% from screening, then the dose of pravastatin is increased to 80 mg daily for the following 6 weeks. | Drug: Pravastatin<br>* Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure<br>* Other names: Pravachol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum aldosterone following angiotensin II infusion |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour urine aldosterone |  | Baseline | 
| 24 hour urine aldosterone |  | 3 months |