Effect of Statin Use on Aldosterone Secretion

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Simvastatin; Other: Placebo; Drug: Pravastatin

• Registration Number: NCT02871687
• Lead Sponsor: Brigham and Women's Hospital

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.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-08-15
• Study First Submitted QC: 2016-08-15
• Study First Posted: 2016-08-18
• Primary Completion: 2021-03
• Study Completion: 2021-03
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-28
• Last Update Posted: 2022-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin	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.
Placebo	Placebo	Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital
Pravastatin	Pravastatin	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.

Primary Outcome Measures

Name	Time	Method
Serum aldosterone following angiotensin II infusion	3 months

Secondary Outcome Measures

Name	Time	Method
24 hour urine aldosterone	3 months

Trial Locations

Locations (1)

Brigham and Women's Hospital- 221 Longwood Avenue; 🇺🇸 Boston, Massachusetts, United States