Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02237079

Acronym

BIM

Enrollment

Registered

2014-09-11

Start date

2014-12-31

Completion date

2018-04-30

Last updated

2023-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Glucose Homeostasis, Obesity, Postmenopausal Symptoms

Brief summary

The goal of this pilot clinical study is to perform a randomized placebo-controlled study to assess the beneficial effect of a 3 month-treatment with Bazedoxifene/Conjugated Estrogens (BZA/CE) vs. placebo on glucose homeostasis and body composition in 20 post-menopausal women. The recruitment will be performed at Tulane Health Sciences Center.

Interventions

DRUGBazedoxifene/Conjugated Estrogens (BZA/CE)

Daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.

DRUGPlacebo Oral Tablet

Daily placebo tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

50 Years to 60 Years

Healthy volunteers

Inclusion criteria

* Post-menopausal women (\<5y since final menstrual period) with age between 50-60y * Symptomatic (hot flashes, vaginal dryness) or asymptomatic * BMI 26-45 kg/m2 (Overweight, Obesity I and Obesity II) * Fasting glucose \<125mg/dl * Triglycerides \<200mg/dl * Normal mammogram within past 12 months * Physician clearance

Exclusion criteria

* Amenorrhea from other causes (Hyperandrogenemia and anovulation) * type 2 and type 1 diabetes * Medications: diabetes or diabetic drugs, dyslipidemia, estrogen/progestin therapy, antidepressants and antipsychotics, antiretroviral (HIV), oral steroids, weight loss drugs * ≤ 3 month washout of birth control pill (often prescribed for postmenopausal symptoms) * Hysterectomy (partial or complete) * Contraindications to estrogen treatment (unusual vaginal bleeding, blot clots, hepatic disease, bleeding disorder, past/present history of breast or uterine cancer, pregnant, breastfeeding)

Design outcomes

Primary

Measure	Time frame	Description
Change in Glucose-stimulated Insulin Clearance (GSIC)	Change at 3 months from baseline	This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT.
Change in Basal Glucose Concentration (Gb)	Change at 3 months from baseline	This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software.
Change in Disposition Index (DI)	Change at 3 months from baseline	Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes.
Change in Insulin Sensitivity (SI) Index	Change at 3 months from baseline	SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.
Change in Homeostatic Model Assessment (HOMA) β-cell Function	Change at 3 months from baseline	The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes.
Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)	Change at 3 months from baseline	Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes.
Change in Fasting Insulin Clearance (FIC)	Change at 3 months from baseline	This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio.
Change in Body Mass Index	Change at 3 months from baseline	Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.
Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio	Change at 3 months from baseline	Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment.
Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)	Change at 3 months from baseline	Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment.
Change in Acute Insulin Response to Glucose (AIRg)	Change at 3 months from baseline	This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.

Secondary

Measure	Time frame	Description
Measure Change in Serum Biomarkers Panel 1	Change at 3 months from baseline	Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months.
Measure Change in Serum Biomarkers Panel 2	Change at 3 months from baseline	Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.
Measure Change in Leptin:Adiponectin Ratio (LAR)	Change at 3 months from baseline	Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.
Measure Change in Fibroblast Growth Factor-21 (FGF-21)	Change at 3 months from baseline	Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months.
Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)	Change at 3 months from baseline	Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months.
Measure Change in C-Reactive Protein (CRP)	Change at 3 months from baseline	Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	7
Placebo Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.	5
Total	12

Baseline characteristics

Characteristic	Placebo	Total	Conjugated Estrogens/Bazedoxifene (CE/BZA)
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	5 Participants	12 Participants	7 Participants
Age, Continuous	55 Years	54.5 Years	54 Years
Body Mass Index (BMI)	31.2 Kg/m^2	32.4 Kg/m^2	33 Kg/m^2
Fasting glucose	88 mg/dL	93.5 mg/dL	94 mg/dL
High-density lipoprotein (HDL)	66 mg/dL	63 mg/dL	60 mg/dL
Low-density lipoprotein (LDL)	128 mg/dL	124 mg/dL	120 mg/dL
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	5 Participants	10 Participants	5 Participants
Region of Enrollment United States	5 participants	12 participants	7 participants
Sex: Female, Male Female	5 Participants	12 Participants	7 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
Total cholesterol	216 mg/dL	211.5 mg/dL	208 mg/dL
Triglycerides	103 mg/dL	113.5 mg/dL	124 mg/dL
Waist circumference	106.7 Cm	108 Cm	109.2 Cm
Waist-to-hip ratio	0.84 Ratio	0.85 Ratio	0.9 Ratio
Years since last menstrual period (LMP)	4.5 Years	2.7 Years	2 Years

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 5
other Total, other adverse events	0 / 7	1 / 5
serious Total, serious adverse events	0 / 7	0 / 5

Outcome results

Primary

Change in Acute Insulin Response to Glucose (AIRg)

This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.