Ignite Creation Date:
2024-05-06 @ 3:39 AM
Last Modification Date:
2024-10-26 @ 11:37 AM
Study NCT ID:
NCT02349945
Status:
COMPLETED
Last Update Posted:
2016-07-12
First Post:
2015-01-16
Brief Title:
FSH Receptor Polymorphism pN680S and Efficacy of FSH Therapy
Sponsor:
Azienda USL Modena
Organization:
Azienda USL Modena
Study Overview
Official Title:
Significance of the FSH Receptor Polymorphism pN680S for the Efficacy of FSH Therapy of Idiopathic Male Infertility a Pharmacogenetic Approach
Status:
COMPLETED
Status Verified Date:
2016-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 pN680S
This is a phase II b multicenter prospective open label one arm clinical trial stratified according to the patients genotype
INTERVENTION FSH therapy 150 IU sc every other day for 12 weeks in infertile men who are homozygous for the wild-type FSHR or the pN680S 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 endpoints pregnancy semen parameters serum levels of inhibin B and AMH
This is a phase II b multicenter prospective open label one arm clinical trial stratified according to the patients genotype
INTERVENTION FSH therapy 150 IU sc every other day for 12 weeks in infertile men who are homozygous for the wild-type FSHR or the pN680S 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 endpoints pregnancy semen parameters serum levels of inhibin B and AMH
Detailed Description:
Male factor infertility is responsible for about 50 of cases of involuntary couple infertility and remains idiopathic in about half of the cases At present there are no consistently effective treatments for male idiopathic infertility Since follicle-stimulating hormone FSH is fundamental for spermatogenesis recombinant hFSH is empirically used for male infertility treatment The response to FSH however is highly variable and while sperm parameters improve in some patients about 50 of the subjects do not clearly respond to FSH Several studies were performed in the past and a recent Cochrane meta-analysis showed that FSH treatment of male idiopathic infertility overall significantly improves pregnancy rate Nevertheless no predictive marker of response to FSH allowing a stratified therapeutic approach was identified so far
The sperm DNA fragmentation index DFI provides an estimation of genetic integrity of spermatozoa and was shown to improve significantly after FSH treatment Therefore DFI could be used as a pharmacodynamic marker of FSH in the male
In women the response to FSH varies depending on the FSH receptor FSHR genotype as determined by the non-synonymous SNP rs6166 which exchanges the amino acid Asn to Ser in codon 680 This SNP is very common with a minor allele frequency of 04 Women homozygous for Ser at amino acid position 680 of the FSHR are less sensitive to endogenous and exogenous FSH compared to those homozygous for Asn and require more FSH for multiple follicular growth and maturation in assisted reproduction The investigators hypothesize that the variable response to FSH in unselected infertile men is due to a different individual sensitivity to FSH as determined by the common FSHR polymorphism rs6166 In particular the investigators will test the hypothesis that men homozygous for Asn at 680 wild type will respond better to exogenous FSH treatment in terms of sperm DFI compared to men homozygous for Ser assessing sperm DFI as pharmacodynamic parameter of FSH
Men with idiopathic infertility and normal serum FSH levels candidate for treatment with FSH will be recruited Men with a sperm DFI 15 will be included in the trial if carriers of the homozygous AsnAsn or SerSer at aminoacid position 680 The FSHR genotype will be assessed centrally and the physician will only receive the information whether the patient is eligible for entering the trial ie homozygous but both the physician and the patient will remain blind to the genotype Human recombinant FSH Gonal-f Merck Serono will be self-administered sc at the dose of 150 IU every other day for 12 weeks followed by 12 weeks of observation follow up Changes in sperm DFI will be the primary end point and compared between the two arms In addition the effects on pregnancy rate and other clinical and hormonal parameters will be evaluated
Should this pilot proof-of-principle trial demonstrate that the response to FSH in male idiopathic infertility depends on FSHR genotype larger interventional trials aiming at assessing the effects on pregnancy rate will be justified
The sperm DNA fragmentation index DFI provides an estimation of genetic integrity of spermatozoa and was shown to improve significantly after FSH treatment Therefore DFI could be used as a pharmacodynamic marker of FSH in the male
In women the response to FSH varies depending on the FSH receptor FSHR genotype as determined by the non-synonymous SNP rs6166 which exchanges the amino acid Asn to Ser in codon 680 This SNP is very common with a minor allele frequency of 04 Women homozygous for Ser at amino acid position 680 of the FSHR are less sensitive to endogenous and exogenous FSH compared to those homozygous for Asn and require more FSH for multiple follicular growth and maturation in assisted reproduction The investigators hypothesize that the variable response to FSH in unselected infertile men is due to a different individual sensitivity to FSH as determined by the common FSHR polymorphism rs6166 In particular the investigators will test the hypothesis that men homozygous for Asn at 680 wild type will respond better to exogenous FSH treatment in terms of sperm DFI compared to men homozygous for Ser assessing sperm DFI as pharmacodynamic parameter of FSH
Men with idiopathic infertility and normal serum FSH levels candidate for treatment with FSH will be recruited Men with a sperm DFI 15 will be included in the trial if carriers of the homozygous AsnAsn or SerSer at aminoacid position 680 The FSHR genotype will be assessed centrally and the physician will only receive the information whether the patient is eligible for entering the trial ie homozygous but both the physician and the patient will remain blind to the genotype Human recombinant FSH Gonal-f Merck Serono will be self-administered sc at the dose of 150 IU every other day for 12 weeks followed by 12 weeks of observation follow up Changes in sperm DFI will be the primary end point and compared between the two arms In addition the effects on pregnancy rate and other clinical and hormonal parameters will be evaluated
Should this pilot proof-of-principle trial demonstrate that the response to FSH in male idiopathic infertility depends on FSHR genotype larger interventional trials aiming at assessing the effects on pregnancy rate will be justified
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None