Effect of Statin Use on Aldosterone Secretion

NCT ID: NCT02871687

Last Updated: 2022-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2021-03-31

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.

Conditions

Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital

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.

Group Type: ACTIVE_COMPARATOR

Simvastatin

Intervention Type: DRUG

Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure

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.

Group Type: ACTIVE_COMPARATOR

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure

Interventions

Simvastatin

Simvastatin 20 mg daily followed by potential increase to 40 mg simvastatin according to dose escalation procedure

Intervention Type: DRUG

Pravastatin

Pravastatin 40 mg daily followed by potential increase to 80 mg pravastatin according to dose escalation procedure

Intervention Type: DRUG

Placebo

Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital

Intervention Type: OTHER

Other Intervention Names

Zocor; Pravachol

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jonathan S. Williams, MD, MMSc

Associate Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Williams, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital- 221 Longwood Avenue

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26432671 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32664962 (View on PubMed)

Other Identifiers

2016P000094

Identifier Type: -

Identifier Source: org_study_id