Advancing Postmenopausal Preventive Therapy

Study Overview
=================
Brief Summary
-----------------
Advancing Postmenopausal Preventive Therapy (APPT) is a randomized, double-blinded, placebo-controlled trial designed to determine the effects of tissue selective estrogen complex (TSEC) therapy on the progression of subclinical atherosclerosis and cognitive decline in 360 healthy postmenopausal women.

Detailed Description
-----------------
To conduct a double-blinded, placebo-controlled trial to determine the effects of TSEC therapy on the progression of subclinical atherosclerosis in healthy postmenopausal women. A total of 360 postmenopausal women with a uterus who are within 6 years of menopause and 45-59 years of age and without clinical cardiovascular disease and diabetes mellitus will be randomized to Bazedoxifene/Conjugated Equine Estrogen (BZA 20 mg/CE 0.45 mg) or placebo. Recruitment will occur over 3 years and the treatment period will be up to 3 years depending on when an individual is randomized. Rate of change in carotid artery intima-media thickness (CIMT) determined from the distal common carotid artery (CCA) far wall intima-media thickness (IMT) in computer image processed B mode ultrasonograms will be the primary trial endpoint. Arterial stiffness measured from the CCA (same location as CIMT) in computer image processed B mode ultrasonograms will be the secondary trial endpoint. Three composite cognitive measures will be used to test for randomized treatment group differences in cognition; each composite will be considered as co-endpoints.

Official Title
-----------------
Atherosclerosis Intervention With Novel Tissue Selective Estrogen Complex Therapy

Conditions
-----------------
Atherosclerosis, Cognitive Decline

Intervention / Treatment
-----------------
* Combination Product: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with a serum estradiol level <30 pg/ml and cessation of regular menses >6 months who are <6 years postmenopausal and 45-59 years old. Exclusion Criteria: Women with a hysterectomy Clinical signs, symptoms or personal history of cardiovascular disease Diabetes mellitus or fasting serum glucose >126 mg/dL Life threatening illness with prognosis <5 years Cirrhosis or liver disease History of deep vein thrombosis or pulmonary embolism History of breast cancer Current use of postmenopausal hormone replacement therapy (HRT) within 1 month of randomization Uncontrolled hypertension (>180/>110 mmHg)* Plasma triglyceride levels >500 mg/dL Serum creatinine >2.0 mg/dL

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 59 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized (1:1), double-blinded, placebo-controlled trial of BZA/CE versus placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BZA/CE<br>Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg | Combination Product: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg<br>* Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg<br>|
| Placebo Comparator: Placebo<br>Oral matching placebo | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid artery intima-media thickness | Rate of change in carotid artery intima-media thickness (CIMT) determined from the distal common carotid artery (CCA) far wall intima-media thickness (IMT) in computer image processed B mode ultrasonograms. | At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CCA stiffness | Arterial stiffness measured from the CCA (same location as CIMT) in computer image processed B mode ultrasonograms. | At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization |