Trial Outcomes & Findings for Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM) (NCT NCT02237079)

NCT ID: NCT02237079

Last Updated: 2023-06-26

Results Overview

Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

17 participants

Primary outcome timeframe

Change at 3 months from baseline

Results posted on

2023-06-26

Participant Flow

Participant milestones

Participant milestones
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Overall Study
STARTED
10
7
Overall Study
COMPLETED
7
5
Overall Study
NOT COMPLETED
3
2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Conjugated Estrogens/Bazedoxifene (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Total
n=12 Participants
Total of all reporting groups
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
White
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=5 Participants
5 Participants
n=7 Participants
12 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
54 Years
n=5 Participants
55 Years
n=7 Participants
54.5 Years
n=5 Participants
Sex: Female, Male
Female
7 Participants
n=5 Participants
5 Participants
n=7 Participants
12 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
7 participants
n=5 Participants
5 participants
n=7 Participants
12 participants
n=5 Participants
Years since last menstrual period (LMP)
2 Years
n=5 Participants
4.5 Years
n=7 Participants
2.7 Years
n=5 Participants
Waist-to-hip ratio
0.9 Ratio
n=5 Participants
0.84 Ratio
n=7 Participants
0.85 Ratio
n=5 Participants
Body Mass Index (BMI)
33 Kg/m^2
n=5 Participants
31.2 Kg/m^2
n=7 Participants
32.4 Kg/m^2
n=5 Participants
Waist circumference
109.2 Cm
n=5 Participants
106.7 Cm
n=7 Participants
108 Cm
n=5 Participants
Fasting glucose
94 mg/dL
n=5 Participants
88 mg/dL
n=7 Participants
93.5 mg/dL
n=5 Participants
Total cholesterol
208 mg/dL
n=5 Participants
216 mg/dL
n=7 Participants
211.5 mg/dL
n=5 Participants
High-density lipoprotein (HDL)
60 mg/dL
n=5 Participants
66 mg/dL
n=7 Participants
63 mg/dL
n=5 Participants
Low-density lipoprotein (LDL)
120 mg/dL
n=5 Participants
128 mg/dL
n=7 Participants
124 mg/dL
n=5 Participants
Triglycerides
124 mg/dL
n=5 Participants
103 mg/dL
n=7 Participants
113.5 mg/dL
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Body Mass Index
-0.2 Kg/m^2
Interval -0.5 to 0.3
-0.5 Kg/m^2
Interval -0.6 to -0.3

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio
-0.05 Ratio
Interval -0.06 to 0.03
0.00 Ratio
Interval -0.02 to 0.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)
Total fat mass
273 g
Interval -571.0 to 974.0
-1408 g
Interval -1932.0 to 467.0
Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)
Visceral adipose tissue (VAT) mass
46 g
Interval -63.0 to 118.0
-47 g
Interval -134.0 to -23.0
Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)
Android fat mass
1.5 g
Interval -226.0 to 611.0
-131 g
Interval -452.0 to -86.0
Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)
Gynoid fat mass
-26 g
Interval -550.0 to 279.0
-178 g
Interval -189.0 to -116.0

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Acute Insulin Response to Glucose (AIRg)
189 uU/l^-1.min^-1
Interval -31.0 to 444.0
-25 uU/l^-1.min^-1
Interval -47.0 to -9.0

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Basal Glucose Concentration (Gb)
-5.2 mg/dL
Interval -9.2 to -1.7
2.7 mg/dL
Interval 0.9 to 4.9

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Disposition Index (DI)
500 Index
Interval -19.0 to 841.0
267 Index
Interval 28.0 to 572.0

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Insulin Sensitivity (SI) Index
-0.24 uU/L^-1.min^-1
Interval -1.5 to 0.19
1.35 uU/L^-1.min^-1
Interval 1.12 to 1.82

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Homeostatic Model Assessment (HOMA) β-cell Function
18.5 uU/mM
Interval -0.9 to 320.6
-25.5 uU/mM
Interval -39.9 to 0.1

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)
0.15 mM.uU/L^-2
Interval -0.18 to 0.34
-0.01 mM.uU/L^-2
Interval -0.1 to 0.24

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Fasting Insulin Clearance (FIC)
-3.50 Ratio
Interval -11.56 to 0.78
-0.25 Ratio
Interval -0.7 to 0.0

PRIMARY outcome

Timeframe: Change at 3 months from baseline

Population: Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).

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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=6 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Change in Glucose-stimulated Insulin Clearance (GSIC)
-32.8 Ratio
Interval -123.6 to 6.9
-1.85 Ratio
Interval -20.5 to 25.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in Serum Biomarkers Panel 1
Leptin
-1.6 ng/mL
Interval -7.2 to 9.5
0.7 ng/mL
Interval -0.1 to 10.5
Measure Change in Serum Biomarkers Panel 1
Lipocalin-2 (LCN2)
-1.7 ng/mL
Interval -3.0 to 3.5
-3.8 ng/mL
Interval -4.9 to 2.2
Measure Change in Serum Biomarkers Panel 1
Plasminogen activator inhibitor-1 (PAI-1)
-1.8 ng/mL
Interval -5.2 to -1.4
1.3 ng/mL
Interval -0.4 to 3.3
Measure Change in Serum Biomarkers Panel 1
Osteocalcin (OCN)
0.8 ng/mL
Interval -0.7 to 3.1
-0.9 ng/mL
Interval -1.1 to 2.7

SECONDARY outcome

Timeframe: Change at 3 months from baseline

Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in Serum Biomarkers Panel 2
Retinol binding protein 4 (RBP4)
-0.4 ug/mL
Interval -5.6 to 14.5
-4.0 ug/mL
Interval -24.1 to 4.6
Measure Change in Serum Biomarkers Panel 2
Adiponectin
-1.4 ug/mL
Interval -2.8 to -0.5
-2.5 ug/mL
Interval -2.6 to -0.4

SECONDARY outcome

Timeframe: Change at 3 months from baseline

Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in Leptin:Adiponectin Ratio (LAR)
2.71 Ratio
Interval -0.04 to 4.96
1.55 Ratio
Interval 0.02 to 4.03

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in Fibroblast Growth Factor-21 (FGF-21)
-134 pg/mL
Interval -208.0 to 24.0
-89 pg/mL
Interval -226.0 to -48.0

SECONDARY outcome

Timeframe: Change at 3 months from baseline

Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in C-Reactive Protein (CRP)
-0.41 mg/mL
Interval -2.66 to 0.45
-0.39 mg/mL
Interval -0.82 to -0.06

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 Participants
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 Participants
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)
-1.7 nmol/mL
Interval -3.3 to -0.4
-1.2 nmol/mL
Interval -1.2 to 0.0

Adverse Events

Bazedoxifene/Conjugated Estrogens (CE/BZA)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Bazedoxifene/Conjugated Estrogens (CE/BZA)
n=7 participants at risk
Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
Placebo
n=5 participants at risk
Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.
Endocrine disorders
Lower Insulin dose given
0.00%
0/7 • The data were collected during baseline visit (during IVGTT for 3 hours) and then again they were collected at the 3 months visit (during IVGTT for 3 hours).
20.0%
1/5 • Number of events 1 • The data were collected during baseline visit (during IVGTT for 3 hours) and then again they were collected at the 3 months visit (during IVGTT for 3 hours).

Additional Information

Dr. Franck Mauvais-Jarvis

Tulane University

Phone: 504-988-5990

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place