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Clinical Relevance of Modifying RANKL Signaling During Folliculogenesis

NCT07546552 · Status: RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 100

Last updated 2026-04-22

No results posted yet for this study

Summary

Female infertility presents a significant societal challenge that will be aggravated in the future due to delayed parenthood. Our translational research suggests that receptor activator of NF-κB ligand (RANKL) is a novel treatment target, during assisted reproductive techniques and that inhibition of this pathway may reduce the impact of aging on the ovary. RANKL is a regulator of bone health, and an antibody (denosumab) blocking RANKL activity is used clinically to treat osteoporosis. Previously, we have shown that inhibition of RANKL increases sperm production in rodents, in human tissue models, and in a subpopulation of infertile men. Now, we show that all factors of the RANKL signalling system are expressed in human and mouse ovaries. Granulosa cell-specific Rankl knockdown lowers the number of primordial follicles, which suggests that RANKL has an important role during early stages of folliculogenesis. Additionally, our data from women undergoing in vitro fertilisation show that follicular fluid concentrations of RANKL and OPG are associated with age and the number of matured follicles, and RANKL inhibition promoted maturation of human oocytes in vitro, which suggests an effect also late in folliculogenesis. Thus, the proposed project aims to: 1) Clarify the role of RANKL in ovaries of mice and humans 2) Determine the reproductive effect of modulating RANKL activity systemically or locally in mice and monkeys 3) Investigate whether manipulation of RANKL can optimise in vitro maturation and rescue of immature human oocytes and 4) Determine whether follicular fluid concentrations of soluble RANKL and OPG may serve as markers of ovarian pathophysiology. The overall aim of this project is to uncover how RANKL regulates follicle reserve and oocyte maturation during the final stages of follicle development. Thereby, determining whether this pathway may be a target for optimisation of IVF treatment and a future treatment option for female infertility.

Conditions

  • Female Infertility
  • NF-κB Ligand
  • RANKL
  • Osteoporosis
  • Follicle Development

Interventions

OTHER

Denosumab

DENOSUMAB facilitates maturation of immature occytes in stage GV and MI

OTHER

PBS

PBS facilitates maturation of immature occytes in stage GV and MI

Sponsors & Collaborators

  • Herlev Hospital

    collaborator OTHER

  • Peter Humaidan

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2025-08-01
Primary Completion
2028-03-15
Completion
2028-03-15

Countries

  • Denmark

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07546552 on ClinicalTrials.gov