Clinical trial NCT04103476: Advancing Postmenopausal Preventive Therapy
Official title: Atherosclerosis Intervention With Novel Tissue Selective Estrogen Complex Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Atherosclerosis
Cognitive Decline
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-09-25
Enrollment: 385
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (1:1), double-blinded, placebo-controlled trial of BZA/CE versus placebo.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Carotid artery intima-media thickness
timeFrame: At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization
Secondary outcomes:
measure: CCA stiffness
timeFrame: At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization
Other outcomes:
measure: Cognitive decline
timeFrame: At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Atherosclerosis Research Unit
state: California
Study officials:
affiliation: University of Southern California Atherosclerosis Research Unit
name: Howard N. Hodis, MD
role: PRINCIPAL_INVESTIGATOR
References: