Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial

Sam Kafai Yahyavi, Rune Holt, Li Juel Mortensen, Jørgen Holm Petersen, Niels Jørgensen, Anders Juul, Martin Blomberg Jensen, Sam Kafai Yahyavi, Rune Holt, Li Juel Mortensen, Jørgen Holm Petersen, Niels Jørgensen, Anders Juul, Martin Blomberg Jensen

Abstract

Background: Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study.

Methods/design: FITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion.

Discussion: We describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need.

Trial registration: Clinical Trials.gov NCT05212337 . Registered on 14 January 2022. EudraCT 2021-003,451-42. Registered on 23 June 2021. Ethical committee H-21040145. Registered on 23 December 2021.

Keywords: Denosumab; Impaired semen quality; Male infertility; Randomized controlled study.

Conflict of interest statement

The authors declare that they have no competing interests except that Martin Blomberg Jensen also is the CEO of “XY Therapeutics.”

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
The expected flow diagram of the progress through the study (CONSORT). Figure legend: An expected CONSORT diagram showing the expected flow of FITMI

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