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

NCT01109979 | Completed Phase 4 Results DMC

• 1 other identifier: 2006p002137
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiovascular Diseases

Keywords

Cardiovascular, vascular

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Estradiol+MPA

ACTIVE COMPARATOR

Drug: Estradiol+MPA

Estradiol+DRSP

ACTIVE COMPARATOR

Drug: Estradiol+Drospirenone

Interventions

Estradiol+MPA DRUG

1 single pill dose daily containing estradiol 1 mg + medroxyprogesterone acetate 2.5 mg

Also known as: Estradiol+medroxyprogesterone acetate

Estradiol+MPA

Estradiol+Drospirenone DRUG

1 single pill dose daily containing estradiol 1mg + drospirenone 0.5 mg

Also known as: Angeliq

Estradiol+DRSP

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy female postmenopausal volunteers, as defined by absence of menses for at least 12 months and follicle stimulating hormone (FSH) 30 IU/L;
• Age 45 to 75 years;
• Systolic blood pressure \<140 and \>90 mmHg and diastolic blood pressure \<90 and \>60 mmHg at the screening visit;
• No personal history of diabetes;
• Body mass index \< 30 kg/m2;
• No clinically significant abnormalities on screening tests (complete blood count, serum electrolytes, liver enzymes, thyroid stimulating hormone, urinalysis, and electrocardiogram).

You may not qualify if:

• Current smoking, defined as smoking within the 12 months before the screening visit;
• Alcohol intake \>1 beverage per night or history of alcohol abuse;
• Current or past recreational drug use;
• 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;
• Risk factors for arterial or venous thromboembolism;
• Personal history of breast cancer or any other type of cancer;
• Personal history of endometrial hyperplasia, endometrial cancer, or unexplained vaginal bleeding;
• History of cervical cancer or abnormal pap smear
• Prescription or herbal medication use, excluding thyroid hormone supplementation;
• Ischemic changes on resting electrocardiogram;
• Serum creatinine ≥ 1.3 mg/dL.
• Serum potassium level \> 5.0 mmol/L;
• Known hypersensitivity to any of the study drugs;
• Other active medical problems detected by examination or laboratory testing, except for treated hypothyroidism.
• Pregnancy

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Bayer: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Lunelle; drospirenone and ethinyl estradiol combination; estradiol-drospirenone combination

Limitations and Caveats

There may have been an order effect of E+DRSP on FMD. For this, however, we would expect %FMD to be lower in the 2nd treatment period, regardless of specific treatment. It is unclear whether this was true cross-over effect or due to the study size.

Results Point of Contact

• Title: Ellen Seely, MD
• Organization: Brigham and Women's Hospital

eseely@partners.org

617-732-5012

Study Officials

• Ellen Seely, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: April 23, 2010
• Study Start: December 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2016
• Last Updated: July 12, 2016
• Results First Posted: May 3, 2013

Record last verified: 2016-06

Locations

US (1)