FITMI - First In Treating Male Infertility

NCT05212337 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 19642021
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This RCT aims to assess whether treatment with Denosumab can improve semen quality in infertile men selected by serum AMH as a positive predictive biomarker.

Conditions

Infertility, Male

Outcome Measures

Primary Outcomes (1)

• The difference in sperm concentration (million pr. mL) on day 80

  Semen analysis - The average concentration of two semen samples delivered on day 80 and day 83 after inclusion is used.

  Day 80 and day 83 after inclusion

Secondary Outcomes (15)

• The difference in semen quality (total sperm count, motile sperm, progressive motile sperm and morphologically normal sperm) between baseline and two semen samples delivered at day 80 and day 83 after inclusion

  Day 80 and day 83 after inclusion

• The differences in pregnancies achieved spontaneously or by IUI before day 180

  Day 180 after inclusion

• The differences in live births where pregnancy is achieved spontaneously or at IUI before day 180

  Day 180 after inclusion

• The differences in number of live births where pregnancy is achieved by artificial insemination (IVF and ICSI) before day 180

  Day 180 after inclusion

• The difference in the number of miscarriages throughout the trial (IVF and ICSI) before day 180

  Day 450 after inclusion

Other Outcomes (17)

• The change in testosterone/estradiol ratio on day 80

  Day 80 after inclusion

• The changes in serum levels of RANKL and OPG on day 80

  Day 80 after inclusion

• The changes in serum levels of OPG on day 80

  Day 80 after inclusion

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

Subcutaneous injection with 60 mg Denosumab once

Drug: Denosumab

Placebo

PLACEBO COMPARATOR

Subcutaneous injection with NaCl once

Drug: Sodium chloride

Interventions

Denosumab DRUG

Subcutaneous injection with 60 mg Denosumab once

Also known as: Prolia

Denosumab

Sodium chloride DRUG

Subcutaneous injection with NaCl once

Also known as: NaCl

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Infertile men ≥ 18 years and \< 60 years of age
• Sperm concentration ≤ 20 million pr. mL
• Serum AMH levels ≥38 pmol/L.
• The participants must have appropriate Danish or English language skills and give written informed consent.

You may not qualify if:

• Chronic diseases, defined as diagnosis where signs, symptoms, and treatment imply an expected long duration and lack of a cure, such as diabetes mellitus, metabolism disorders, osteoporosis, colitis, etc.
• Sperm concentration \<2 million pr. mL
• Men with current or previous malignancies, or at potential risk of testicular cancer after baseline examination and ultrasound will be excluded.
• Men with hypocalcemia at baseline, defined as ionized calcium of \< 1,18 mmol/L or albumin corrected calcium \< 2,17 mmol/L or total calcium \< 2.14 mmol/L
• Serum vitamin D (25OHD) levels \< 25 nmol/L
• eGFR \< 60 mL/min/1,73 m2
• Insufficient dental status
• Vasectomy
• Semen volume \< 0.9 mL
• Hypersensitivity to latex, Denosumab, or to any of the excipients (acetic acid, sodium hydroxide, Sorbitol (E420), Polysorbate 20) will be excluded.

Sponsors & Collaborators

• Martin Blomberg Jensen: lead

Study Sites (1)

Department of Growth and Reproduction, Rigshospitalet

Copenhagen, Denmark

Location

Related Publications (31)

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• Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jorgensen N. Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Mar 1;103(3):870-881. doi: 10.1210/jc.2017-01656.

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• Juel Mortensen L, Lorenzen M, Jorgensen N, Andersson AM, Nielsen JE, Petersen LI, Lanske B, Juul A, Hansen JB, Blomberg Jensen M. Possible link between FSH and RANKL release from adipocytes in men with impaired gonadal function including Klinefelter syndrome. Bone. 2019 Jun;123:103-114. doi: 10.1016/j.bone.2019.03.022. Epub 2019 Mar 23.

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• Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol. 2014 Mar;10(3):175-86. doi: 10.1038/nrendo.2013.262. Epub 2014 Jan 14.

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• Anastasilakis AD, Toulis KA, Polyzos SA, Terpos E. RANKL inhibition for the management of patients with benign metabolic bone disorders. Expert Opin Investig Drugs. 2009 Aug;18(8):1085-102. doi: 10.1517/13543780903048929.

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• Makras P, Polyzos SA, Papatheodorou A, Kokkoris P, Chatzifotiadis D, Anastasilakis AD. Parathyroid hormone changes following denosumab treatment in postmenopausal osteoporosis. Clin Endocrinol (Oxf). 2013 Oct;79(4):499-503. doi: 10.1111/cen.12188. Epub 2013 Apr 1.

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• Schwarz P, Rasmussen AQ, Kvist TM, Andersen UB, Jorgensen NR. Paget's disease of the bone after treatment with Denosumab: a case report. Bone. 2012 May;50(5):1023-5. doi: 10.1016/j.bone.2012.01.020.

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• Polyzos SA, Singhellakis PN, Naot D, Adamidou F, Malandrinou FC, Anastasilakis AD, Polymerou V, Kita M. Denosumab treatment for juvenile Paget's disease: results from two adult patients with osteoprotegerin deficiency ("Balkan" mutation in the TNFRSF11B gene). J Clin Endocrinol Metab. 2014 Mar;99(3):703-7. doi: 10.1210/jc.2013-3762. Epub 2014 Jan 16.

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• Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Man Z, Mellstrom D, Radominski SC, Reginster JY, Resch H, Roman Ivorra JA, Roux C, Vittinghoff E, Austin M, Daizadeh N, Bradley MN, Grauer A, Cummings SR, Bone HG. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res. 2012 Mar;27(3):694-701. doi: 10.1002/jbmr.1479.

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• Boonen S, Adachi JD, Man Z, Cummings SR, Lippuner K, Torring O, Gallagher JC, Farrerons J, Wang A, Franchimont N, San Martin J, Grauer A, McClung M. Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab. 2011 Jun;96(6):1727-36. doi: 10.1210/jc.2010-2784. Epub 2011 Mar 16.

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• Sohn W, Lee E, Kankam MK, Egbuna O, Moffat G, Bussiere J, Padhi D, Ng E, Kumar S, Slatter JG. An open-label study in healthy men to evaluate the risk of seminal fluid transmission of denosumab to pregnant partners. Br J Clin Pharmacol. 2016 Feb;81(2):362-9. doi: 10.1111/bcp.12798. Epub 2015 Dec 5.

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• Jorgensen A, Blomberg Jensen M, Nielsen JE, Juul A, Rajpert-De Meyts E. Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model. J Steroid Biochem Mol Biol. 2013 Jul;136:238-46. doi: 10.1016/j.jsbmb.2012.10.008. Epub 2012 Oct 23.

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• Yahyavi SK, Holt R, Jorsal MJ, Wall-Gremstrup G, Toft FB, Juel Mortensen L, Nohr B, Melsen LM, Praetorius L, Nielsen HS, Pinborg A, Beck Jensen JE, Schwarz P, Bennedbaek FN, Aksglaede L, Jorgensen A, Jorgensen N, Petersen JH, Juul A, Blomberg Jensen M. Effect of denosumab on semen quality in infertile men selected by serum level of antimullerian hormone: a randomized controlled trial. Fertil Steril. 2025 Oct;124(4):668-678. doi: 10.1016/j.fertnstert.2025.05.151. Epub 2025 May 20.

  PMID: 40403914 DERIVED

• Holt R, Yahyavi SK, Wall-Gremstrup G, Jorsal MJ, Toft FB, Jorgensen N, Juul A, Blomberg Jensen M. Low-serum antimullerian hormone is linked with poor semen quality in infertile men screened for participation in a randomized controlled trial. Fertil Steril. 2024 Aug;122(2):278-287. doi: 10.1016/j.fertnstert.2024.03.018. Epub 2024 Mar 24.

  PMID: 38522503 DERIVED

• Yahyavi SK, Holt R, Juel Mortensen L, Petersen JH, Jorgensen N, Juul A, Blomberg Jensen M. Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial. Trials. 2022 Jun 22;23(1):525. doi: 10.1186/s13063-022-06478-4.

  PMID: 35733213 DERIVED

MeSH Terms

Conditions

Infertility, Male

Interventions

Denosumab; Sodium Chloride

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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Sam Kafai Yahyavi, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Rune Holt, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: groups designated with X and Y
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Model Details: Interim analysis will be forward to study committee to evaluate data and decide whether study should proceed to be stopped

Study Record Dates

• First Submitted: January 3, 2022
• First Posted: January 28, 2022
• Study Start: January 1, 2022
• Primary Completion: October 22, 2024
• Study Completion: September 30, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)