NAPO - Novel Approach for Oligospermia

NCT06300229 | Completed Phase 1 DMC

• 1 other identifier: 2023-508325-27-00
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled trial aims to assess whether treatment with denosumab can improve semen quality in infertile men selected by serum anti-mullerian hormone (AMH) as a positive predictive biomarker, and with severely impaired semen quality (concentrations between 0.01 million/mL to 2 million/mL).

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 (7)

• 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 change/differences in number of pregnancies achieved before day 180

  Day 180 after inclusion

• The difference in the number of miscarriages throughout the trial before day 180

  Day 450 after inclusion]

• The change/difference in serum levels of follicle stimulating hormone (FSH) on day 80

  Day 80 after inclusion

• The change/difference in serum levels of reproductive hormone luteinizing hormone (LH) on day 80

  Day 80 after inclusion

Other Outcomes (2)

• The change/difference in CatSper expression on day 80

  Day 80 after inclusion

• The change/difference in RANKL expression 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: sodium chloride (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 ≤ 2 million pr. mL
• Serum AMH levels ≥28 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 \<0.01 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 albumin corrected calcium \< 2,17 mmol/L or total calcium \< 2.14 mmol/L
• Serum vitamin D (25OHD) levels \< 25 nmol/L
• estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min/1,73 m2
• Insufficient dental status
• Vasectomy
• Hypersensitivity to latex, Denosumab, or to any of the excipients (acetic acid, sodium hydroxide, Sorbitol (E420), Polysorbate 20) will be excluded.
• Serum FSH \<3 IU/L
• Testis size \> 17 mL
• BMI ≥ 35 kg/m2

Sponsors & Collaborators

• Martin Blomberg Jensen: lead

Study Sites (1)

Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine

Copenhagen, Denmark

Location

Related Publications (31)

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• Yahyavi SK, Jorsal MJ, Holt R, Nohr B, Blomberg Jensen M. Novel approach for oligospermia (NAPO) - Protocol for a randomized controlled trial. Contemp Clin Trials Commun. 2024 Aug 22;41:101352. doi: 10.1016/j.conctc.2024.101352. eCollection 2024 Oct.

  PMID: 39280787 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

  Division of Translational Endocrinology, Herlev, Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: Head of Research Department Endocrinology

Study Record Dates

• First Submitted: March 2, 2024
• First Posted: March 8, 2024
• Study Start: March 1, 2024
• Primary Completion: January 29, 2025
• Study Completion: August 31, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)