Effects of Novel Estrogens on Glucose and Lipids in Postmenopausal Prediabetic Women Veterans

NCT ID: NCT05073237

Last Updated: 2024-05-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-08
• Study Completion Date: 2024-04-08

Brief Summary

The purpose of this study is to determine the effect of a novel menopause hormone therapy on blood sugar (glucose) and blood and liver fats (lipids) in obese menopausal women Veterans.

Detailed Description

Menopause is a natural process characterized by estrogen deficiency that results in several undesirable metabolic changes, including increase in body fat, decrease in lipid oxidation, impairment in glucose tolerance, and hyperinsulinemia. One in four women dies of cardiovascular disease (CVD), and with the increase in life expectancy, many women will spend almost half of their lives in a postmenopausal state of estrogen deficiency that predisposes them to metabolic syndrome, hyperlipidemia (HLD) and type 2 diabetes (T2D) resulting in overall increased risk for CVD. Menopausal hormone therapy (MHT) is beneficial if administered in early menopausal women, age 50-60 years . The most promising and novel MHT involves the combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) in a single tablet. The major innovation of CE/BZA is that it provides all the advantages of CE treatment without the use and side effects of a progestin. Moreover, an important beneficial effect of estrogen is also to prevent postmenopausal metabolic disorders . One of the most comprehensive research initiatives undertaken on the postmenopausal health of women, The Women's Health Initiative (WHI), involved nearly 4,000 women Veterans. The studies from WHI show how military service affects women's longevity and overall health as compared to non-Veterans. The data from WHI shows that women Veterans have higher all-cause mortality rates than non-Veterans and higher hip fracture rates despite similar risk factors. Also, women Veterans <65 years at WHI enrollment were more likely to have experienced prior hysterectomy and early hysterectomy before age 40 compared with non-Veterans.

Additionally, information about the effectiveness of CE/BZA as MHT in women with abnormal glucose is lacking. In that regard, there is a critical need to determine the effects of CE/BZA on beta cell function in obese menopausal women with early glucose abnormalities, primarily in the pre-diabetes and early diabetes stages, and prevent evolution toward full-blown diabetes as these women are at higher risk for CVD.

In the current study, 40 women Veterans with obesity, prediabetes and menopause who are experiencing bothersome menopause symptoms will be enrolled and randomized to receive either 16 weeks of CE/BZA or 16 weeks of placebo to find the effect of the drug on glucose and lipids metabolism.

Conditions

Menopause; Prediabetes; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

conjugated estrogens/bazedoxifene (CE/BZA)

Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. Recommended and only FDA approved dosage is one CE/BZA tablet daily, taken without regard to meals. Tablets should be swallowed whole. If a dose of BZA/CE is missed, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications.

Group Type: EXPERIMENTAL

conjugated estrogens/bazedoxifene (CE/BZA)

Intervention Type: DRUG

Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20mg.

Placebo

Participants assigned to placebo will receive a daily tablet. To assure the blind is maintain, participants in the placebo group will be given the same instructions for taking the study medication. Tablets should be swallowed whole. If a dose, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about CE/BZA and its potential side effects and contraindications, again to maintain the blind.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Daily placebo tablet

Interventions

Placebo

Daily placebo tablet

Intervention Type: OTHER

conjugated estrogens/bazedoxifene (CE/BZA)

Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20mg.

Intervention Type: DRUG

Other Intervention Names

DUAVEE

Eligibility Criteria

Inclusion Criteria

Postmenopausal women veterans within 5 years of menopause.

Menopause is defined as:

• women with intact uterus and last menstrual period >1 year ago but <5 years ago
• Age 50-60 years
• BMI 27-34.9kg/m2 (Overweight and low risk Class 1 Obesity)
• Symptomatic (moderate to severe vasomotor symptoms)
• Fasting glucose 100-150mg/dl or/or HbA1c >5.7%- and <7% (two abnormal test can be fasting glucose or HbA1c or combination of the two in the past 6 months).
• Triglycerides < 200 mg/dl
• GFR >60mL/min
• Normal mammogram within the past 12 months

Exclusion Criteria

• Amenorrhea from other causes (Hyperandrogenemia and anovulation)
• Recent weight change (>10 lbs in the last 3 months), intended or unintended
• Vulnerable populations (employees, students, individuals with impaired decision making capacity, pregnant women, prisoners, terminally ill, and children)
• Change in lipid lowering agent in the last 3 months
• Use of glucose lowering agents in the last 3 months
• Concurrent conditions including HIV, uncontrolled hyperthyroidism, uncontrolled hypothyroidism or less than 3 months since addition or change in thyroid hormone modulating medications, current use of drugs known to promote significant weight changes, menopause hormone therapy use within 3 months
• Contraindications to estrogens (history of thromboembolic disorder, coronary artery or cerebrovascular disease, clotting disorders (Antiphospholipid antibody syndrome, protein C deficiency, protein S deficiency, AT III deficiency, factor V leiden), severe liver disease, history of breast or uterine cancer or unexplained vaginal bleeding)
• Plan for major surgery or prolonged immobilization within 6 month period
• MRI Absolute contraindications

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dragana Lovre, MD

Role: PRINCIPAL_INVESTIGATOR

Southeast Louisiana Veterans Health Care System, New Orleans, LA

Locations

Southeast Louisiana Veterans Health Care System, New Orleans, LA

New Orleans, Louisiana, United States

Countries

United States

Other Identifiers

1IK2CX002225-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ENDA-009-20F

Identifier Type: -

Identifier Source: org_study_id