Advancing Postmenopausal Preventive Therapy (APPT)

Atherosclerosis Intervention With Novel Tissue Selective Estrogen Complex Therapy

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.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis; Cognitive Decline
• Intervention / Treatment: Other: Placebo; Combination product: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg

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 Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lora Maxwell, RN; Phone Number: (323) 442-2257; Email: APPT@usc.edu
• Study Contact Backup: Name: Janie Teran; Phone Number: (323) 442-1478; Email: athero@usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California Atherosclerosis Research Unit
      • Contact: Lora Maxwell, RN; Phone Number: 323-442-2257; Email: APPT@usc.edu
      • Contact: Janie Teran; Phone Number: 323-442-1478; Email: athero@usc.edu
      • Principal Investigator: Howard N. Hodis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BZA/CE; Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg	Combination product: Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg; Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg
Placebo Comparator: Placebo; Oral matching placebo	Other: Placebo; Placebo

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive decline	Three composite cognitive measures will be used to test for randomized treatment group differences in cognition; each composite will be considered as co-endpoints.	At baseline and 6 months, 1 year, 1.5 years, 2 years, 2.5 years and 3 years after randomization

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Howard N. Hodis, MD, University of Southern California Atherosclerosis Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Anticipated): October 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Atherosclerosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: R01AG058691 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No