Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function

Cardiovascular Diseases Clinical Trial

Official title:

Effect of Combined Estradiol and Drospirenone Treatment Versus Combined Estradiol and Medroxyprogesterone Acetate Treatment on Endothelial Function: A Crossover Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109979
• Other study ID #: 2006p002137
• Status: Completed
• Phase: Phase 4
• First received: April 22, 2010
• Last updated: June 9, 2015
• Start date: December 2009

Study information

• Verified date: June 2015
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study compares the effects of two common hormone medications on the heart and blood vessels of healthy post-menopausal women over the age of 45.

The study will take place over the course of about 5 months. Each subject will take two different medications over two six-week periods. They will be randomized at the beginning of the study to either estradiol+medroxyprogesterone acetate or estradiol+drospirenone for the first period, and will receive the other medication the second six-weeks of the study. At the very beginning of the study and at the end of each six-week treatment period, subjects will come to the hospital various tests including non-invasive blood vessel imaging tests, blood draws to test the levels of certain hormones in the body, an oral glucose tolerance test, a test to monitor renal blood flow, and 24-hour blood pressure monitoring. Between treatment periods, there will be a four-week medication-free washout period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Healthy female postmenopausal volunteers, as defined by absence of menses for at least 12 months and follicle stimulating hormone (FSH) 30 IU/L;

2. Age 45 to 75 years;

3. Systolic blood pressure <140 and >90 mmHg and diastolic blood pressure <90 and >60 mmHg at the screening visit;

4. No personal history of diabetes;

5. Body mass index < 30 kg/m2;

6. No clinically significant abnormalities on screening tests (complete blood count, serum electrolytes, liver enzymes, thyroid stimulating hormone, urinalysis, and electrocardiogram).

Exclusion Criteria:

1. Current smoking, defined as smoking within the 12 months before the screening visit;

2. Alcohol intake >1 beverage per night or history of alcohol abuse;

3. Current or past recreational drug use;

4. Personal history of hypertension, cardiovascular disease (coronary artery disease, congestive heart failure, valvular heart disease, stroke, transient ischemic attack, or intermittent claudication), hyperlipidemia, diabetes (defined as a fasting glucose =126 mg/dL), kidney disease, liver disease, venous or arterial thromboembolic disease, adrenal insufficiency, depression, or illness requiring overnight hospitalization in the past 6 months;

5. Risk factors for arterial or venous thromboembolism;

6. Personal history of breast cancer or any other type of cancer;

7. Personal history of endometrial hyperplasia, endometrial cancer, or unexplained vaginal bleeding;

8. History of cervical cancer or abnormal pap smear

9. Prescription or herbal medication use, excluding thyroid hormone supplementation;

10. Ischemic changes on resting electrocardiogram;

11. Serum creatinine = 1.3 mg/dL.

12. Serum potassium level > 5.0 mmol/L;

13. Known hypersensitivity to any of the study drugs;

14. Other active medical problems detected by examination or laboratory testing, except for treated hypothyroidism.

15. Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• Estradiol+MPA
1 single pill dose daily containing estradiol 1 mg + medroxyprogesterone acetate 2.5 mg
• Estradiol+Drospirenone
1 single pill dose daily containing estradiol 1mg + drospirenone 0.5 mg

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD)	This crossover study examined the effects of E+MPA versus E+DRSP on brachial artery reactivity (BAR) assessed after six weeks of treatment. BAR is a noninvasive measure of endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. With this technique, inflation of an arm blood pressure cuff to suprasystolic blood pressure causes relative ischemia downstream to the cuff. Upon deflation, a brief state of increased blood flow occurs (reactive hyperemia), and the resulting increase in shear stress causes nitric oxide release and resulting vasodilation of the brachial artery (flow-mediated vasodilation). The flow-mediated changes in brachial artery diameter can be imaged by ultrasound and measured as an index of peripheral vasomotor function. BAR correlates with invasive assessments of coronary endothelial function as well as multiple cardiovascular risk factors.	%FMD after 6 weeks of treatment	No