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Evaluating the Roles of Estrogen and Progesterone in Heart Metabolism (Estrogen)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00565916
Recruitment Status : Terminated (Atypically high dropout rate.)
First Posted : November 30, 2007
Results First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Robert Wood Johnson Foundation
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies have shown that the breakdown of fatty acids in cardiac muscle is important in maintaining a healthy heart, and that estrogen may enhance this process. Also, cardiovascular disease (CVD) occurs more frequently in postmenopausal women than in premenopausal women. This study will determine in postmenopausal women whether estrogen increases the heart's ability to use fats as energy and whether progesterone decreases this effect.

Condition or disease Intervention/treatment Phase
Postmenopausal Syndrome Drug: Estrogen Drug: Progesterone Drug: Placebo Not Applicable

Detailed Description:

Menopause is a natural event that generally occurs in women between the ages of 45 and 55. During menopause, the body starts producing less estrogen and progesterone until menstruation eventually stops. Estrogen and progesterone are involved in many important functions in a woman's body, and the drastic decline of these hormones in menopause leads to significant changes in the body. Along with such changes, postmenopausal women are at a higher risk than premenopausal women for certain health problems, such as CVD. Previous studies have revealed that alterations in the breakdown of fatty acids in cardiac muscle play a key role in a variety of cardiac disorders. In studies involving human skeletal muscle, estrogen has been shown to increase the breakdown of fatty acids, while progesterone lessens this effect. This study will determine in postmenopausal women whether estrogen increases the heart's ability to break down fats for energy use and whether progesterone decreases this effect. This study will also analyze ovariectomized mice to determine if the candidate specific estrogen receptor modulators (SERMs) raloxifene and tamoxifen increase the heart's ability to use fats as energy and whether the increase is similar to that seen with estrogen. Study investigators will also create estrogen receptor knock-out mice (mice with estrogen receptors removed) to further explore the roles of estrogen and SERMs in heart metabolism.

Participation in this double-blind study will last up to 1 month and will include three study visits. During Visit 1, participants will undergo three standard clinical evaluations. The first evaluation, a medical screening, will include a medical history exam and blood tests to measure estrogen and progesterone levels, liver and kidney function, cholesterol levels, and blood sugar and insulin levels. For the second evaluation, participants will undergo a body composition study to measure total body fat and muscle content using a dual-energy x-ray absorptiometry (DEXA) scan. During the third evaluation, participants will undergo an electrocardiogram (ECG) and an echocardiogram (ECHO), each performed immediately before and after walking on a treadmill. The ECG will measure electrical activity of the heart, and the ECHO will involve imaging the heart with an ultrasound.

Visits 2 and 3, occurring 3 days apart, will each include two imaging tests of the heart: a positron-emission tomographic (PET) scan and a resting ECHO. Throughout both tests an ECG and blood pressure cuff will be used to monitor heart rhythm and blood pressure, respectively. During the PET scan, participants will lie flat in an imaging machine for three 45- to 60- minute intervals. Blood will be drawn and radioactive tracers will be injected via intravenous lines placed in the arms. The ECHO test will also be done during the PET scan.

Between Visits 2 and 3, participants will be randomly assigned to one of two hormone replacement therapy (HRT) regimens: estrogen plus placebo or estrogen plus progesterone. All participants will wear a patch containing estrogen and take a pill of either placebo or progesterone for the 3 days leading up to Visit 3. All participants will be asked for permission to store a sample of their blood for up to 10 years to be used in future research studies.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Role of Estrogen/SERMS on Cardiac Fatty Acid Metabolism (Aim #1- Human Studies)
Study Start Date : August 2004
Actual Primary Completion Date : January 2008
Actual Study Completion Date : January 2008

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: estrogen plus progesterone
Hormone replacement therapy (HRT): estrogen plus progesterone
Drug: Estrogen

Estrogen only plus placebo: estradiol topical patch 0.3 mg placed on the lower abdomen for 3 days plus an oral placebo.

Other procedures: heart metabolism tests which includes a positron-emission tomography (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).

Other Name: Estradiol

Drug: Progesterone
Estrogen plus progesterone: estradiol with oral progesterone (Prometrium, 200 mg/day) for 3 days, instead of placebo. Progesterone therapy involves taking a daily oral pill of 200 mg Prometrium for the same 3 days that the estradiol is taken.
Other Name: prometrium

Active Comparator: estrogen plus placebo
Hormone replacement therapy (HRT): estrogen plus placebo
Drug: Estrogen

Estrogen only plus placebo: estradiol topical patch 0.3 mg placed on the lower abdomen for 3 days plus an oral placebo.

Other procedures: heart metabolism tests which includes a positron-emission tomography (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).

Other Name: Estradiol

Drug: Placebo
Placebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken.
Other Name: Inactive Drug




Primary Outcome Measures :
  1. Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization. [ Time Frame: 3 days ]
    Measurements of myocardial fatty acid utilization and oxidation with C[11]-Palmitate and PET in healthy postmenopausal women who take either estrogen alone or with progesterone. The primary outcome measure was designed to determine prospectively whether estrogen will increase the heart's fatty acid utilization and whether progestins will attenuate this effect, in a manner similar to what was seen in an observational study of hormone replacement therapy (HRT) in post-menopausal women. To this end, we had anticipated enrolling 30 healthy post-menopausal women for assessment of cardiac fatty acid metabolism using positron emission tomography (PET) and radioactive C[11]-Palmitate both before and after 3 days of hormone replacement therapy. These volunteers were to be randomized to receive either estrogen alone (E) or combined estrogen/progesterone (EP).



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy postmenopausal woman
  • Body mass index less than 30
  • Practices normal eating habits
  • Stops hormone replacement therapy at least 6 months prior to study entry

Exclusion Criteria:

  • Currently taking hormone replacement therapy
  • History of cardiovascular disease
  • Family history of coronary artery disease
  • Recent history of smoking, high blood pressure, or hyperlipidemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00565916


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63366
Sponsors and Collaborators
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Robert Wood Johnson Foundation
Investigators
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Principal Investigator: Pablo Soto, MD Washington University Medical School

Publications:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00565916    
Other Study ID Numbers: 489
K23HL077179 ( U.S. NIH Grant/Contract )
IRB# 04-0812 ( Other Identifier: IRB )
RDRC# 538F ( Other Identifier: RDRC )
GCRC# 966 ( Other Identifier: GCRC )
First Posted: November 30, 2007    Key Record Dates
Results First Posted: October 16, 2018
Last Update Posted: October 16, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Washington University School of Medicine:
Post-Menopausal
PET
Estrogen
Progesterone
Heart Metabolism
Cardiovascular Disease
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Estrogens
Progesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins