CE/BZA: Effects of Novel Estrogens on Glucose and Lipids in Postmenopausal Prediabetic Women Veterans

Sponsor
VA Office of Research and Development (U.S. Fed)
Overall Status
Not yet recruiting
CT.gov ID
NCT05073237
Collaborator
(none)
40
Enrollment
1
Location
2
Arms
35
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Other: Placebo
  • Drug: conjugated estrogens/bazedoxifene (CE/BZA)
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
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.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.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
randomized, double blind, placebo-controlled trial
Primary Purpose:
Treatment
Official Title:
Effects of Novel Estrogens on Glucose and Lipids in Postmenopausal Prediabetic Women Veterans
Anticipated Study Start Date :
Jan 17, 2022
Anticipated Primary Completion Date :
Jan 15, 2024
Anticipated Study Completion Date :
Dec 16, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

Drug: conjugated estrogens/bazedoxifene (CE/BZA)
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20mg.
Other Names:
  • DUAVEE
  • Placebo Comparator: 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.

    Other: Placebo
    Daily placebo tablet

    Outcome Measures

    Primary Outcome Measures

    1. change in beta cell function [Change in beta cell function between baseline and 16 weeks]

      beta cell function will be evaluated via oral glucose tolerance test at baseline and after 16 weeks of treatment.

    Secondary Outcome Measures

    1. change in liver fat [Change in Liver fat between baseline and 16 weeks]

      Change in liver fat will be evaluated via MRI-PDFF between baseline and after 16 weeks of treatment.

    2. change in serum lipidomics [Change in serum lipidomics between baseline and 16 weeks]

      Change in serum lipidomics will be evaluated via UPLC-MS/MS at baseline and after 16 weeks of treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 60 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Southeast Louisiana Veterans Health Care System, New Orleans, LANew OrleansLouisianaUnited States70112

    Sponsors and Collaborators

    • VA Office of Research and Development

    Investigators

    • Principal Investigator: Dragana Lovre, MD, Southeast Louisiana Veterans Health Care System, New Orleans, LA

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    VA Office of Research and Development
    ClinicalTrials.gov Identifier:
    NCT05073237
    Other Study ID Numbers:
    • ENDA-009-20F
    • 1IK2CX002225-01A1
    First Posted:
    Oct 11, 2021
    Last Update Posted:
    Oct 11, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by VA Office of Research and Development
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 11, 2021