NCT04067726

RANKL Inhibition and Mammographic Breast Density

Randomized Clinical Trial of RANKL Inhibition With Denosumab on Mammographic Density in Premenopausal Women With Dense Breasts (TRIDENT)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 210 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: Female
• Age: 40 Years
• Healthy volunteers: Not accepted

Summary

Data supporting a role for RANKL signaling in mammographic density and breast cancer development has begun to emerge, but clinical trial data providing definitive evidence that would allow the adoption of RANKL inhibition in primary breast cancer prevention are not yet available. The hypothesis is that RANKL inhibition with denosumab will decrease mammographic density in high-risk premenopausal women with dense breasts. To address this, the investigators have developed this clinical trial to quantify the impact of RANKL inhibition on mammographic density in high-risk premenopausal women with dense breasts and to determine the effect of RANKL inhibition on markers of proliferation and biomarkers of breast cancer risk. Successful demonstration that RANKL inhibition reduces mammographic density could open up additional approaches to primary breast cancer prevention in high-risk premenopausal women, who do not have dominant genetic predisposition.

Conditions

• Dense Breasts

Interventions

Type	Name	Description
DRUG	Denosumab	Denosumab is commercially available and will be provided at no cost to participants.
DRUG	Placebo	Placebo will be made available as 1 mL sterile, non-pyrogenic water solution in a single-use prefilled syringe.
DRUG	Calcium	-Participants will be instructed to take calcium (at least 500 mg) daily for 12 months between baseline examination and 12- month mammographic breast density examination.
DRUG	Vitamin D3	Participants will be instructed to take vitamin D3 (at least 400 IU) supplements daily for 12 months between baseline examination and 12- month mammographic breast density examination.
PROCEDURE	Core needle biopsy	Baseline and 12 months
PROCEDURE	Blood draw	Baseline and 12 months

Timeline

• Start date: 2019-08-27
• Primary completion: 2025-09-17
• Completion: 2026-08-31
• First posted: 2019-08-26
• Last updated: 2026-03-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study