FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy

NCT02349945 | Completed Phase 2 DMC

• 1 other identifier: EudraCT 2010-020240-35
• Study Type: interventional
• Target: 88
• Locations: 2 countries
• Sites: 6

Brief Summary

CONDITION: Idiopathic male infertility In men with idiopathic infertility, the sperm DNA fragmentation index (DFI) within 12 weeks of FSH therapy and 12 weeks follow-up improves depending on the FSHR genotype as assessed by the non-synonymous SNP rs6166 (wild type or p.N680S). This is a phase II b, multicenter, prospective, open label, one arm, clinical trial stratified according to the patient's genotype. INTERVENTION: FSH therapy (150 I.U. sc every other day for 12 weeks) in infertile men who are homozygous for the wild-type FSHR or the p.N680S allele of the FSHR. Duration of intervention per patient: 12 weeks Primary efficacy endpoint: Sperm DFI. Number of patients with an improvement in DFI \> 60% Key secondary endpoint(s): pregnancy, semen parameters, serum levels of inhibin B and AMH.

Conditions

Male Infertility

Outcome Measures

Primary Outcomes (1)

• Sperm DFI

  "after 12 weeks"

Secondary Outcomes (2)

• Sperm DFI (DNA Fragmentation Index)

  "Baseline"

• Sperm DFI

  "after 24 weeks"

Other Outcomes (12)

• Pregnancy rate

  "baseline"

• Pregnancy rate

  "After 12 weeks"

• Pregnancy rate

  "after 24 weeks"

Study Arms (2)

Arm 1

EXPERIMENTAL

FSHR A680G SNP homozygous for allele N treated with follitropin alpha

Drug: follitropin alpha

Arm 2

EXPERIMENTAL

FSHR A680G SNP homozygous for allele S treated with follitropin alpha

Drug: follitropin alpha

Interventions

follitropin alpha DRUG

All subjects included in the study will receive recombinant FSH therapy (follitropin alpha: Gonal-f 150 I.U. s.c. every other day for 12 weeks). Follow up: 12 further weeks after end of treatment. Previous studies included in the Cochrane meta-analysis used: hMG/hCG, 150 IU three times a week for 13 weeks; purified FSH, 150 IU/day for 12 weeks; rec hFSH, 150 IU/day for 12 weeks; rec hFSH, 100 IU on alternate days for 3 months. Therefore any dosage \> 100 IU on alternate days is eligible. The duration of treatment is based on the duration of one spermatogenetic cycle.

Also known as: Gonal f

Arm 1; Arm 2

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age 20-50 years
• idiopathic male factor infertility for at least one year;
• homozygous FSHR allele at codon 680 (wild type: Asn/Asn or Ser/Ser);
• sperm DFI \> 15%;
• normal serum FSH levels (\< 8 IU/L)
• normal serum LH, testosterone, prolactin and estradiol levels
• normal ovulatory female partner These men might have impaired ejaculate parameters (decreased sperm count and/or decreased proportion of sperm with progressive motility and/or decreased proportion of sperm with normal morphology) of unknown aetiology.

You may not qualify if:

• azoospermia
• all known aetiologies of male infertility (endocrine disorders, genetic disorders, chromosome abnormalities, congenital bilateral absence of the vas deferens, microdeletions within the AZF regions of the Y chromosome, varicocele, cryptorchidism, infections, immunological infertility, and obstructive infertility)
• all known aetiologies of female infertility in the partner (tubal blockage, endocrine abnormalities including anovulation and PCO, anatomical abnormalities, infections)
• heterozygous FSHR allele at codon 680
• drug abuse and major systemic diseases
• testicular insufficiency

Sponsors & Collaborators

• Azienda USL Modena: lead
• University of Roma La Sapienza: collaborator
• University of Halle Medical Faculty: collaborator
• Istituto Clinico Humanitas: collaborator
• University of Padova: collaborator
• University of Florence: collaborator

Study Sites (6)

Zentrums für Reproduktions-medizin und Andrologie Universitätsklinikum Halle (Saale), Martin-Luther-Universität Halle-Wittenberg

Halle, 06120, Germany

Location

Dipartimento di Ginecologia e Medicina della Riproduzione IRCCS Istituto Clinico Humanitas,

Rozzano, Milan, 20089, Italy

Location

Andrology Unit Department of Clinical Physiopathology

Florence, 50139, Italy

Location

AziendaUSLModena

Modena, 41126, Italy

Location

University of Padova Department of Histology, Microbiology and Medical Biotechnologies Clinical Pathology Section & Centre for Male Gamete Cryopreservation

Padua, 35121, Italy

Location

Department of Medical Pathophysiology, University of Rome La Sapienza, Lab of Seminology & Immunology of Reproduction

Rome, Italy

Location

MeSH Terms

Conditions

Infertility, Male

Interventions

Glycoprotein Hormones, alpha Subunit; follitropin alfa

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chorionic Gonadotropin; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Manuela Simoni, MD, PhD

  Azienda USL Modena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: January 29, 2015
• Study Start: January 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2015
• Last Updated: July 12, 2016

Record last verified: 2016-07

Locations

DE (1); IT (5)