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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital |
|
| Simvastatin | Active Comparator | 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. |
|
| Pravastatin | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| Serum aldosterone following angiotensin II infusion | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| 24 hour urine aldosterone | Baseline | |
| 24 hour urine aldosterone | 3 months |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan Williams, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital- 221 Longwood Avenue | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26432671 | Background | Baudrand R, Pojoga LH, Vaidya A, Garza AE, Vohringer PA, Jeunemaitre X, Hopkins PN, Yao TM, Williams J, Adler GK, Williams GH. Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects. Circulation. 2015 Nov 10;132(19):1825-33. doi: 10.1161/CIRCULATIONAHA.115.016759. Epub 2015 Oct 2. | |
| 32664962 | Derived |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| D017035 | Pravastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Pravastatin | Drug | Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure |
|
|
| Placebo | Other | Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital |
|
| Hornik ES, Altman-Merino AE, Koefoed AW, Meyer KM, Stone IB, Green JA, Williams GH, Adler GK, Williams JS. A clinical trial to evaluate the effect of statin use on lowering aldosterone levels. BMC Endocr Disord. 2020 Jul 14;20(1):105. doi: 10.1186/s12902-020-00587-4. |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |