Female InfertilityNCT07546552
Clinical Relevance of Modifying RANKL Signaling During Folliculogenesis
A study testing Denosumab and PBS in people with Female Infertility and NF-κB Ligand, run by Peter Humaidan at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Female Infertility, NF-κB Ligand, RANKL
- What is being tested?
- Denosumab and PBS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2025to 15 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Female in the age of 18 or above, Normal AMH-value, able to give concent
Who cannot join
- Patients who have had autotransplanted ovarian tissue
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Regionshospitalet, Skive, Midt Jylland 7800
Skive, Midt Jylland, 7800
Peter Humaidan PH Professior, Professor, +4578445760, peter.humaidan@midt.rm.dk
About this study
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
- Being tested
- Denosumab, PBS
- Medical subject headings
- Infertility, Female, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabOther
DENOSUMAB facilitates maturation of immature occytes in stage GV and MI
PBSOther
PBS facilitates maturation of immature occytes in stage GV and MI
| Study group | Role | What they receive |
|---|---|---|
| Study group | Experimental | DENOSUMAB medical preparation Receives: Other: Denosumab |
| Control group | Active comparator | PBS medical preparation Receives: Other: PBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate and compare the reproductive phenotype of granulosa cell-specific Rankl knock down mice, global Rankl knock out mice, and a humanized RANKL mouse model treated with denosumab.
Measured: From enrollment to the end of the study
Investigate the effects of manipulating RANKL activity on ovarian function in human adult ovaries ex vivo and in xenotransplanted human ovarian cortex tissue.
Measured: From enrollment to the end of the study
Investigate the reproductive effect of pharmacological RANKL inhibition in higher primates
Measured: From enrollment to the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study start1 Aug 2025
- Primary completion15 Mar 2028 (estimated)
- Study completion15 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter Humaidan
- Sponsor type
- University, hospital or other
- Collaborators
- Herlev Hospital
- Responsible party
- Sponsor-investigator, Peter Humaidan, Regionshospitalet Viborg, Skive
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07546552
- Sponsor's protocol ID
- RANKL
- Status last verified
- Apr 2026
- First submitted
- 26 Mar 2026
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Relevance of Modifying RANKL Signaling During Folliculogenesis
- ClinicalTrials.gov ID
- NCT07546552
- Acronym / sponsor ID
- RANKL
- Conditions
- Female Infertility, NF-κB Ligand, RANKL, Osteoporosis, Follicle Development
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Peter HumaidanUniversity, hospital or other
- Collaborators
- Herlev Hospital
- Study start
- 1 Aug 2025 (actual)
- Primary completion
- 15 Mar 2028 (estimated)
- Study completion
- 15 Mar 2028 (estimated)
- First posted
- 22 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study group | Experimental | Other: DenosumabDENOSUMAB medical preparation |
| Control group | Active comparator | Other: PBSPBS medical preparation |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Female in the age of 18 or above, Normal AMH-value, able to give concent
Key exclusion criteria (1 listed)
- Patients who have had autotransplanted ovarian tissue
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabDENOSUMAB facilitates maturation of immature occytes in stage GV and MI | Other | Study group |
| PBSPBS facilitates maturation of immature occytes in stage GV and MI | Other | Control group |
Primary outcome
Evaluate and compare the reproductive phenotype of granulosa cell-specific Rankl knock down mice, global Rankl knock out mice, and a humanized RANKL mouse model treated with denosumab.
Time frame: From enrollment to the end of the study
Investigate the effects of manipulating RANKL activity on ovarian function in human adult ovaries ex vivo and in xenotransplanted human ovarian cortex tissue.
Time frame: From enrollment to the end of the study
Investigate the reproductive effect of pharmacological RANKL inhibition in higher primates
Time frame: From enrollment to the end of the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Denosumab and PBS in people with Female Infertility and NF-κB Ligand, run by Peter Humaidan at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate and compare the reproductive phenotype of granulosa cell-specific Rankl knock down mice, global Rankl knock out mice, and a humanized RANKL mouse model treated with denosumab. (time frame: From enrollment to the end of the study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.