Denosumab and Male Infertility: a RCT

NCT03030196 | Completed Phase 2 DMC

• 2 other identifiers: 011120162016-003546-84
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility, Male

Outcome Measures

Primary Outcomes (1)

• Change in semen production (total motile spermatozoa, progressive motile spermatozoa, spermatozoa-count, spermatozoa-concentration)

  semen analysis

  80 days and 160 days after intervention

Secondary Outcomes (18)

• Change in semen quality (-motility, -morphology of semen volume)

  80 days,160 days after intervention

• Change in DNA fragmentation (DFI) in spermatozoa

  80 days after intervention

• Change in serum Inhibin-B concentration

  80 days and 160 days after intervention

• Change in serum levels of reproductive hormonea (FSH, LH, AMH, testosterone, estradiol inhibin B/FSh ratio and SHBG)

  80 days and 160 days after intervention

• Change in bone mineral density evaluated by DXA

  80 days and 160 days after intervention

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

subcutaneous injection with 60 mg Denosumab once

Drug: Denosumab

Placebo

PLACEBO COMPARATOR

subcutaneous injection with NaCl once

Drug: Denosumab

Interventions

Denosumab DRUG

NaCl 0.9% injection is used as placebo

Also known as: Prolia

Denosumab; Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men \> 18 years of age refered due to infertility in need for further investigation with
• Sperm count \> 0,05 mio./ml.
• The men have either sperm count \<15 mio./ml or
• \<40 % motile spermatozoer (A) or
• \<4 % morphological normale spermatozoer (strict criteria)

You may not qualify if:

• Men with chronic diseases (diabetes mellitus, thyroid disease, endocrine diseases requiring treatment, malignant diseases or diseases known to be affected by- or interfere with vitamin D supplements (granulomatous diseases such as sarcoidosis, tuberculosis, wegeners, vasculitis as well as inflammatory bowel diseases e.g. chron's disease or ulcerative colitis etc).
• Men with active or previous malignant disease
• Any case with indication for tesis biopsy,
• Serum ionized calcium \< 1,15 mmol/l
• Total calcium \< 2.14 mmol/l
• Poor dental status og dental implants
• Men with obstructive oligospermia or who has been vasectomized
• Serum Inhibin B \< 30 pg/ml
• Abnormal karyotype
• Patients practising excessive exercise

Sponsors & Collaborators

• Martin Blomberg Jensen: lead

Study Sites (1)

Department of Growth and Reproduction, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (25)

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• Yahyavi SK, Holt R, Juel Mortensen L, Boisen IM, Arting LB, Jorgensen A, Juul A, Blomberg Jensen M. Effect of a single-dose denosumab on mineral homeostasis in infertile men: insights from a pilot intervention study and a randomized controlled trial. BMC Med. 2025 Mar 7;23(1):145. doi: 10.1186/s12916-025-03958-7.

  PMID: 40055742 DERIVED

MeSH Terms

Conditions

Infertility, Male

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Li J Mortensen, MD

  Rigshospitalet, Dpt. of Growth and Reproduction, section GR 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

• martin Blomberg Jensen, MD

  Rigshospitalet, Dpt. of Growth and Reproduction, section GR 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: January 1, 2017
• Primary Completion: January 1, 2021
• Study Completion: May 1, 2023
• Last Updated: June 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)