Effect of Statin Use on Aldosterone Secretion

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Other: Placebo; Drug: Simvastatin; Drug: Pravastatin

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 Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital- 221 Longwood Avenue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital	Other: Placebo; Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital
Active Comparator: 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.	Drug: Simvastatin; Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure; Other Names: Zocor
Active Comparator: 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.	Drug: Pravastatin; Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure; Other Names: Pravachol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
24 hour urine aldosterone	Baseline
24 hour urine aldosterone	3 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Jonathan Williams, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin; Simvastatin
• Other Study ID Numbers: 2016P000094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No