Atherosclerosis Intervention With Novel Tissue Selective Estrogen Complex Therapy
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 385
- Locations
- 1
- Primary Endpoint
- Carotid artery intima-media thickness
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Randomization randomly determined with key to treatment groups maintained by a single individual in the data coordinating center (DCC); study product masked with matching placebo.
Eligibility Criteria
- Ages
- 45 Years to 59 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
BZA/CE
Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg
Intervention: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg (Combination Product)
Placebo
Oral matching placebo
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Carotid artery intima-media thickness
Time Frame: At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization
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.
Secondary Outcomes
- CCA stiffness(At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization)
Investigators
Howard N. Hodis, M.D.
Professor of Medicine and Preventive Medicine, Director Atherosclerosis Research Unit
University of Southern California