Advancing Postmenopausal Preventive Therapy

Phase 2

Active, not recruiting

• Conditions: Atherosclerosis; Cognitive Decline
• Interventions: Other: Placebo; Combination Product: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg

• Registration Number: NCT04103476
• Lead Sponsor: University of Southern California

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 Timeline

• Study First Submitted: 2019-09-20
• Study First Submitted QC: 2019-09-23
• Study First Posted: 2019-09-25
• Study Start: 2021-04-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-05
• Primary Completion: 2026-10-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 385

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral matching placebo
BZA/CE	Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg	Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg

Primary Outcome Measures

Name	Time	Method
Carotid artery intima-media thickness	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 Outcome Measures

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

Trial Locations

Locations (1)

University of Southern California Atherosclerosis Research Unit; 🇺🇸 Los Angeles, California, United States