Estrogen Diastolic Heart Failure

Phase 4

Terminated

Conditions: Menopause

Interventions: Drug: Estradiol/Norethindrone acetate
Drug: Placebo

Registration Number: NCT02693002

Lead Sponsor: Gretchen Wells

Brief Summary: Peri-menopausal women will be randomized to hormone replacement therapy or placebo for 12 weeks to determine if markers of systolic and diastolic function change by echocardiography as well as laboratory markers of heart failure, including b-type natriuretic peptide (BNP).

Detailed Description: This preliminary, feasibility study will randomize 28 peri-menopausal women to either hormone replacement therapy or placebo for 12 weeks. Prior to randomization, each participant will undergo echocardiography, measurements of activity using the Duke Activity Status Index, measurements of quality of life and laboratory data, including b-type natriuretic peptide (BNP) measurements. Following the intervention for 12 weeks, these measurements will all be repeated.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 4

Inclusion Criteria

28 healthy recently postmenopausal women with last menstrual bleeding 12 months at study entry. Women with last menstrual bleeding within 12 months at study entry are those who are peri-menopausal and for whom the drug is FDA approved.

Exclusion Criteria

History of hysterectomy, oophorectomy or both
History of heart disease including cardiac transplantation, heart failure, bypass surgery or percutaneous intervention, and valve disease defined as moderate or severe valve regurgitation or stenosis
History of bone disease including non-traumatic vertebral fractures on radiography
Uncontrolled chronic disease (including uncontrolled diabetes defined as a hemoglobin A1C >8, uncontrolled hypertension defined as a systolic blood pressure >160 mmHg, awaiting organ transplant)
Previous or current cancer, excluding basal cell carcinoma
Previous or current thromboembolic disease
Previous intolerance of Hormone replacement therapy (HRT) or Oral contraception (OC)
Current or previous use of HRT within the past 3 months
Current or recent (<12 months) substance abuse, including tobacco use
No drug interactions with HRT
No racial or ethnic groups will be excluded

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hormone replacement therapy	Estradiol/Norethindrone acetate	Estradiol/norethindrone acetate 1mg/0.5 mg by mouth oral daily for 12 weeks
Placebo	Placebo	Inert ingredients by mouth oral daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Diastolic Function Assessed by Echocardiography	Baseline and 12 weeks	Change in diastolic function as assessed by echocardiography from baseline to 12 weeks

Secondary Outcome Measures

Name	Time	Method
Quality of Life Score Assessed by Utian Quality of Life Scale (UQoLS)	Baseline and 12 weeks	Change in quality of life score as assessed by Utian Quality of Life scale. The UQoLS measures quality of life in four subcategories: Occupational, health, emotional and sexual. Questions are scored on a scale of 1-5 were 1 indicates "Not true of me" and 5 indicates an answer of "mostly true". Scores to the responses are added and evaluated within each subcategory. Higher scores indicate a higher quality of life within each subcategory with a maximum of 35 points for "Occupational", 31 points for "Health", 28 points for "Emotional" and 15 points for "Sexual" for a total of 100 points indicating the highest quality of life score possible. Data will be presented as the change in quality of life Mean +/- SEM over time.
B-type Natriuretic Peptide (BNP) Levels	Baseline and 12 weeks	Change in B-type natriuretic peptide (BNP) levels will be measure. Participants will have blood drawn via venipuncture and B-type natriuretic peptide will be measured using a quantitative chemiluminescent immunoassay. Data will be presented as the change in B-type natriuretic peptide over time.
Activity Level Assessed by Duke Activity Status Index (DASI)	Baseline and 12 weeks	Change in activity level as assessed by Duke Activity Status Index. The DASI estimates functional capacity through a series of 12 questions related to daily activity. Questions are scored as zero for a "No" answer or awarded a fixed number of points ranging from 1.75-8 for a "Yes" answer. Scores for each question are added, with the maximum score being 58.2 indicating a fully functional individual. Data are presented as the change in Mean score +/- SEM for each group at baseline and 12 weeks.