Clinical Trial: Denosumab and Male Infertility: a RCT

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Denosumab and Male Infertility: a Randomized Controlled Double-blinded Intervention Study

Brief Summary: To determine the significance of systemic RANKL inhibition for male reproduction, conducting a clinical controlled randomized double blinded intervention study on infertile men, to investigating whether Denosumab (Prolia) can increase semen quality and to investigate what subgroup of infertile men that might benefit from treatment.

Detailed Summary:

INTRODUCTION

Infertility is a serious problem estimated to affect 7-26% of all couples globally (1;2). Approximately 9% of all newborns were conceived by assisted reproductive techniques in 2013 in Denmark (Danish Fertility Society). Impaired semen quality is the causal or contributing factor in almost 50% of all cases of infertility (3;4). Today, there exist no treatments that can improve semen quality of most infertile men. Instead, the vast majority of infertile couples are treated with assisted reproductive techniques (ART) independently of the aetiology (maternal/paternal) causing the infertility (3;5-8). The treatment choice ranges from mild intrauterine inseminations (IUI) to more invasive in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). ART is successful for more than 70% of all couples. However, ART is very expensive and associated with maternal side effects due to the invasive methodology and the need for hormonal treatment, often for several months (9-11). Infertility is also a financial burden to society due to the costs of ART to maintain an acceptable annual birth rate.

Fertility potential determined by semen quality is established already as a fetus (12). In case the testes don't develop normally, reduced semen quality in adulthood will be the result as a result of impaired Sertoli cell function. Up until today it has barely been investigated whether intervention during adulthood can improve semen quality.

Our recent studies using both human testis and Vitamin D receptor knock-out mice revealed that the vitamin D regulated bone factor RANKL is expressed in the testis (13;14). This is a novel finding, because up until now RANKL has only been known to affect bone homeostasis and to some extend influence the immune system, inflammation an
Sponsor: Martin Blomberg Jensen

Current Primary Outcome: Change in semen production (total motile spermatozoa, progressive motile spermatozoa, spermatozoa-count, spermatozoa-concentration) [ Time Frame: 80 days and 160 days after intervention ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in semen quality (-motility, -morphology of semen volume) [ Time Frame: 80 days,160 days after intervention ]
  • Change in DNA fragmentation (DFI) in spermatozoa [ Time Frame: 80 days after intervention ]
  • Change in serum Inhibin-B concentration [ Time Frame: 80 days and 160 days after intervention ]
  • Change in serum levels of reproductive hormonea (FSH, LH, AMH, testosterone, estradiol and SHBG) [ Time Frame: 80 days and 160 days after intervention ]
  • Change in bone mineral density evaluated by DXA [ Time Frame: 80 days and 160 days after intervention ]
  • • Change in serum level of inactive vitamin D, 1,25(OH)2D3, 25-OHD3, 24,25(OH)2D3, PTH, alkaline phosphatase, ionized calcium, phosphate, FGF23, Klotho, osteocalcin [ Time Frame: 80 days and 160 days after intervention ]
  • Change in choice of assisted reproductive assistance technique as well as conceived pregnancies [ Time Frame: 80 days,160 days and 365 days after intervention ]
  • Change in spontaneous conception rate. [ Time Frame: 80 days,160 days and 365 days after intervention ]
  • Change in number of spermatozoa expressing RANKL [ Time Frame: 80 days and 160 days after intervention ]
  • Change in semen pH, HCO3-, calcium, zink, phosphate, RANKL, RANK, OPG, FGF23, Klotho, osteocalcin, osteopontin. [ Time Frame: 80 days and 160 days after intervention ]
  • Difference in infection rate in the two groups [ Time Frame: 80 days and 160 days after intervention ]
  • Change in serum level of osteopontin, calcitonin, pnp, procollagen III, OPG, RANKL, Sclerostin as well as other bone marker [ Time Frame: 80 days and 160 days after intervention ]
  • Change in live birth rate [ Time Frame: 80 days,160 days and 365 days after intervention ]


Original Secondary Outcome:

  • Change in semen quality (-motility, -morphology og semenvolume) [ Time Frame: 80 days,160 days after intervention ]
  • Change in DNA fragmentation (DFI) in spermatozoa [ Time Frame: 80 days after intervention ]
  • Change in serum Inhibin-B concentration [ Time Frame: 80 days and 160 days after intervention ]
  • Change in serum levels of reproductive hormonea (FSH, LH, AMH, testosterone, estradiol and SHBG) [ Time Frame: 80 days and 160 days after intervention ]
  • Change in bone mineral density evaluated by DXA [ Time Frame: 80 days and 160 days after intervention ]
  • • Change in serum level of inactive vitamin D, 1,25(OH)2D3, 25-OHD3, 24,25(OH)2D3, PTH, alkaline phosphatase, ionized calcium, phosphate, FGF23, Klotho, osteocalcin [ Time Frame: 80 days and 160 days after intervention ]
  • Change in choice of assisted reproductive assistance technique as well as conceived pregnancies [ Time Frame: 80 days,160 days and 365 days after intervention ]
  • Change in spontaneous conception rate. [ Time Frame: 80 days,160 days and 365 days after intervention ]
  • Change in number of spermatozoa expressing RANKL [ Time Frame: 80 days and 160 days after intervention ]
  • Change in semen pH, HCO3-, calcium, zink, phosphate, RANKL, RANK, OPG, FGF23, Klotho, osteocalcin, osteopontin. [ Time Frame: 80 days and 160 days after intervention ]
  • Difference in infection rate in the two groups [ Time Frame: 80 days and 160 days after intervention ]
  • Change in serum level of osteopontin, calcitonin, pnp, procollagen III, OPG, RANKL, Sclerostin as well as other bone marker [ Time Frame: 80 days and 160 days after intervention ]
  • Change in live birth rate [ Time Frame: 80 days,160 days and 365 days after intervention ]


Information By: Rigshospitalet, Denmark

Dates:
Date Received: January 20, 2017
Date Started: January 2017
Date Completion: January 2021
Last Updated: March 23, 2017
Last Verified: March 2017