SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02349945

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Significance of the FSH Receptor Polymorphism p.N680S for the Efficacy of FSH Therapy of Idiopathic Male Infertility: a Pharmacogenetic Approach

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.

NCT02349945 Male Infertility
MeSH: Infertility Infertility, Male
HPO: Infertility Male infertility

1 Interventions

Name: follitropin alpha

Description: 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.

Type: Drug

Arm 1 Arm 2


Primary Outcomes

Measure: Sperm DFI

Time: "after 12 weeks"

Secondary Outcomes

Measure: Sperm DFI (DNA Fragmentation Index)

Time: "Baseline"

Measure: Sperm DFI

Time: "after 24 weeks"

Other Outcomes

Measure: Pregnancy rate

Time: "baseline"

Measure: Pregnancy rate

Time: "After 12 weeks"

Measure: Pregnancy rate

Time: "after 24 weeks"

Measure: Sperm count

Time: "baseline"

Measure: Sperm count

Time: "after 12 weeks"

Measure: Sperm count

Time: "after 24 weeks

Description: Serum dosage

Measure: Inhibin B

Time: "baseline"

Description: Serum dosage

Measure: Inhibin B

Time: "after 12 weeks"

Description: Serum dosage

Measure: Inhibin B

Time: "after 24 weeks"

Description: Serum dosage of Anti-Mullerian Hormone

Measure: Anti-Mullerian Hormone (AMH)

Time: "baseline"

Description: Serum dosage of Anti-Mullerian Hormone

Measure: AMH

Time: "after 12 weeks"

Description: Serum dosage of Anti-Mullerian Hormone

Measure: AMH

Time: "after 24 weeks"

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 rs6166

FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy 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).

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.

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.



HPO Nodes


HPO:
Infertility
Genes 133
HJV MKRN3 SOX3 SNORD115-1 SOX9 AMH PATL2 PLCZ1 AMHR2 KLHL10 WDR66 MAGEL2 CFAP300 SRA1 ZMPSTE24 WWOX LHX4 GCM2 STUB1 DNAAF4 TUBB8 AXL DAZ4 CYP19A1 RBMY1A1 CFTR DUSP6 TSGA10 GATA4 WT1 MEIOB CCNO IPW PWRN1 CDH23 POU1F1 SRY DAZ1 NDN LRRC6 CFAP43 TSPY1 H6PD HUWE1 TEX14 NR3C1 USP9Y TEX11 CCDC141 GBA2 ZP3 QRICH2 CFAP298 CDC14A AR CCDC39 AK7 SNORD116-1 HESX1 FGF17 MAP3K1 ZFPM2 PGR MKRN3-AS1 DNAH1 FANCA DNAJB13 LHCGR ZP1 FSIP2 DNAAF5 DNAAF3 DNAI1 AURKC USP8 SLC26A8 PTPN11 OTX2 POLR3B CATSPER1 FOXL2 DMRT3 DHH LMNA BRAF CATSPER2 BRDT ZMYND10 RSPH1 ADGRG2 WDR11 FEZF1 GLI2 SPATA16 FSHB SPRY4 VAMP7 NR0B1 SUN5 DNAI2 NPAP1 TLE6 SOHLH1 RNF216 DDX3Y PIH1D3 WEE2 NR5A1 FLRT3 CTNS PWAR1 STRC HERC2 HSD17B3 DAZ3 DAZ2 DNAAF1 PLIN1 CFAP44 MAP2K1 IL17RD DNAH9 NANOS1 GNRH1 GNRHR SNRPN PRLR SEPTIN12 PMFBP1 CEP19 PROP1 SEMA3E CCDC40
Male infertility
Genes 41
GATA4 WT1 LHCGR SOX9 DNAAF5 DNAI1 AURKC AMH AMHR2 DDX3Y SRY DAZ1 NR5A1 PTPN11 CTNS CATSPER1 TSPY1 STRC DMRT3 WWOX DAZ3 USP9Y GCM2 TEX11 DAZ2 BRAF CATSPER2 MAP2K1 ADGRG2 DAZ4 CYP19A1 RBMY1A1 MAP3K1 ZFPM2 CFTR PMFBP1 VAMP7 NR0B1 SUN5 DNAI2 FANCA