New treatment for men with non-obstructive azoospermia

Novel Treatment of Some Men With Non-Obstructive Azoospermia (NT-NOA): A Clinical Interventional Study

This study is testing a new treatment using two medications to see if it can help men with non-obstructive azoospermia produce more sperm.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 60 Years
• Sex: Male
• Sponsor: Copenhagen University Hospital at Herlev (other)
• Drugs / interventions: Denosumab
• Locations: 1 site (Herlev)
• Trial ID: NCT06706414 on ClinicalTrials.gov

What this trial studies

This clinical interventional study evaluates the effectiveness of denosumab combined with letrozole in enhancing sperm production in infertile men diagnosed with non-obstructive azoospermia. Participants will be selected based on serum anti-mullerian hormone (AMH) levels, which serve as a predictive biomarker for treatment response. The study aims to address the significant gap in treatment options for men with this condition, as traditional methods often yield limited success. By exploring this novel combination therapy, the study seeks to provide a potential solution for a largely underserved patient population.

Who should consider this trial

Good fit: Ideal candidates are infertile men aged 18 to 60 with azoospermia and normal semen volume, who have no identifiable obstruction.

Not a fit: Patients with chronic diseases, chromosome anomalies, or previous malignancies are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the chances of biological fatherhood for men suffering from non-obstructive azoospermia.

How similar studies have performed: While this approach is novel, other studies have explored hormonal treatments for male infertility, but specific outcomes for non-obstructive azoospermia remain largely untested.

Eligibility criteria

Inclusion Criteria:

* Infertile men ≥ 18 years and \< 60 years of age with azoospermia with normal semen volume (\> 0.9 mL) verified by minimum 2 semen samples.
* Testis size (Prader Orchidometer) ≤ 15 mL on both sides.
* No identifiable cause of obstruction.
* Serum AMH levels ≥5 pmol/L.

Exclusion Criteria:

* 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.
* Chromosome anomalies e.g. Klinefelter Syndrome, XX male
* AZFa/b/c microdeletions besides b2/b3 og gr/gr
* Detected CFTR mutation
* 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
* Hypersensitivity to latex, Denosumab, or to any of the excipients (acetic acid, sodium hydroxide, Sorbitol (E420), Polysorbate 20) will be excluded.
* Serum Inhibin B \< 5 pg/mL
* Androgen replacement therapy
* Hypogonadotropic hypogonadism
* BMI ≥ 35 kg/m2

Where this trial is running

Herlev

• Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Herlev and Gentofte Hospital — Herlev, Denmark (RECRUITING)

Study contacts

• Principal investigator: Christian F.S. Jensen, MD, PhD. — Department of Urology, Herlev and Gentofte Hospital
• Study coordinator: Mads Joon Jorsal, MD

Conditions: Infertility, Male