SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01378299

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

CYP19A1 Gene and Pharmacogenetics of Response

Testosterone (T) replacement prevents bone loss and relieves symptoms associated with androgen deficiency in male patients with hypogonadism, but at the expense of an increase in prostate-related adverse events and in the hematocrit values above the normal which may lead to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This project is designed to determine if genetic variations in the CYP19A1 gene will result in differences in the skeletal response and incidence of side effects from T treatment in patients with low T. A large number of male Veterans are on T. Results from this project will help identify patients who would benefit from the therapy from those at risk for side effects, and would definitely have an impact in the future care of these patients and male patients in general once genetic profiling becomes part of the standard of care.

NCT01378299 Hypogonadism
MeSH: Hypogonadism
HPO: Gonadotropin deficiency Hypergonadotropic hypogonadism Hypogonadism Hypogonadotrophic hypogonadism

1 Interventions

Name: Testosterone Cypionate

Description: Testosterone cypionate was administered at 200 mg by intramuscular injection every 2 weeks. DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight of 412.61.

Type: Drug

Arm 1: Testosterone Cypionate


Primary Outcomes

Description: Percent change in bone mineral density from baseline to 18 months

Measure: Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene

Time: form baseline to 18 months

Description: Percent change in bone mineral density from baseline to 18 months.

Measure: Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene

Time: baseline to 18 months

Secondary Outcomes

Description: Percent changes in bone mineral density from baseline

Measure: Percent Change in Bone Mineral Density According to Body Mass Index (BMI)

Time: baseline to 18 months

Description: Percent change in PSA from baseline to 18 months

Measure: Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene

Time: From baseline to 18 months

Description: Percent change in PSA from baseline at 18 months

Measure: Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene

Time: from baseline to 18 months

Description: Percent change in hematocrit from baseline to 18 months

Measure: Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene

Time: baseline to 18 months

Description: Percent change in hematocrit from baseline to 18 months

Measure: Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene

Time: Baseline to 18 months

Description: Percent change in gene expression from baseline to 18 months

Measure: Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene

Time: Baseline to 6 months

Description: Percent change in bone turnover from baseline to 18 months.

Measure: Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene

Time: Baseline to 18 months

Description: Percent change in bone turnover markers

Measure: Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene

Time: Baseline to 18 months

Description: Percent change in bone mineral density from baseline to 18 months

Measure: Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus

Time: Baseline to 18 months

Description: Percent change in bone turnover markers from baseline to 18 months.

Measure: Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus

Time: Baseline to 18 months

Purpose: Other

Single Group Assignment


There are 2 SNPs

SNPs


1 rs1062033

Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene.

Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene.

Percent change in bone turnover from baseline to 18 months.. Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene.


2 rs700518

Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene.

Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene.

Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene.



HPO Nodes


HPO:
Gonadotropin deficiency
Genes 9
GLI3 PCSK1 POMC FGFR1 CHD7 LHX3 FSHB SEMA3E KISS1R
Hypergonadotropic hypogonadism
Genes 51
CLPP FANCC FANCD2 FANCE LHCGR SOX9 MRE11 FANCB BMPR1B SLC29A3 POLR3B ZBTB20 SAMD9 DMRT3 WWOX GALT LMNA ALMS1 AMACR CYP17A1 RRM2B CYP19A1 POLG RIN2 POLR1C VAMP7 NR0B1 CTDP1 GATA4 DCAF17 WT1 AHSG SCP2 TWNK SRY NR5A1 GNAS TYMP COQ2 ITGB6 LEP LEPR MAP3K1 SIL1 ZFPM2 CYB5A POLR3A BMP15 MGME1 PMM2 FANCA
Hypogonadism
Genes 349
CLPP SOX2 MKRN3 PCSK1 SOX3 MKKS GABRD CDKN1C SNORD115-1 SPATA7 HFE SOX9 SOX10 CERKL PRPF31 LRAT IFT140 ARL2BP ERCC1 SLC29A3 ERCC2 MAK AHI1 ERCC3 BRIP1 ABCA4 LZTR1 ERCC4 PDE4D ZBTB20 ERCC5 PDE6A SAMD9 ERCC6 PDE6G ZMPSTE24 WWOX IMPDH1 GALT STUB1 ATRX TRAF3IP1 PDE6B AXL IFT172 AMACR KIZ CYP17A1 CDHR1 INPP5K CYP19A1 SDCCAG8 DHX38 HDAC8 PTDSS1 GATA4 IPW PEX1 BBS1 PWRN1 PEX6 BBS2 CDH23 BBS4 DHDDS SRY NDN PRPF6 PLXND1 AGBL5 RRAS DCC GPR101 PTCH1 COQ2 BCS1L BBS9 DDB2 TUB ITGB6 ALX4 PHGDH SNORD116-1 HESX1 FGF17 MAP3K1 MKS1 TULP1 CHRNG RNU4ATAC MEN1 SNAP29 FANCA SLC52A3 FANCC FANCD2 FANCE SEMA3A ARL6 TTC8 ERCC8 PROM1 FANCB BMP4 FANCF FANCG NEK2 BMPR1B GJB2 ANOS1 PTPN11 SAG KISS1R DMRT3 PNPLA6 DHH BRCA1 ALMS1 BRAF BRCA2 PROKR2 KLHL7 REEP6 FAM161A SGPL1 GLI2 HS6ST1 RIN2 RAB3GAP2 RECQL4 A2ML1 NECTIN1 VAMP7 NR0B1 NPAP1 SCAPER FSCN2 DCAF17 AHR AHSG PRCD SCP2 ANTXR1 RNF216 FGF8 NTN1 TAC3 FGFR1 TACR3 ABCD1 FLRT3 GNAS PWAR1 SEMA4A MAD2L2 HERC2 SLC52A2 MERTK HSD17B3 DMPK DMRT1 KISS1 USH2A CLRN1 CNGB1 CNGA1 GNRH1 GNRHR ALG1 CA4 IMPG2 PDE11A CBX2 PMM2 HJV RAD51 RAD51C CUL4B PROK2 NPHP1 KRAS RAF1 MRE11 IFT27 BEST1 PSAT1 DMXL2 NR2E3 MAGEL2 SRA1 FMR1 NRAS LHX4 ANK1 OFD1 RASA2 NRL CLIP2 CISD2 WFS1 IFT74 POLD1 POLE SMCHD1 RRM2B POLG DUSP6 LZTFL1 CEP290 POLR1C RBP3 WRN HGSNAT KCNAB2 WT1 BBIP1 AIRE KIAA1549 PHF6 BAZ1B RDH12 POMGNT1 POU1F1 PRPH2 ARHGEF18 DNM1L TWNK PCARE SLC39A4 FANCL XPA CHD7 XPC SIN3A AIP BBS5 RBM28 IDH3B REV3L XRCC2 RFC2 FANCM GTF2IRD1 SKI TYMP PRPF8 CCDC141 RGR SLC7A14 PREPL AR LEP OPA1 WDPCP LEPR PALB2 SIL1 ZFPM2 PPM1B RFWD3 SLC3A1 POLR3A RHO CRB1 BBS10 MKRN3-AS1 TFR2 CRX SIX6 RIT1 TGFB1 RLBP1 CNBP LHB LHCGR MRPS7 DNAL4 LIMK1 EYS RAB3GAP1 ARL3 IGF1 OTX2 POLR3B GTF2I STS NSMF ARSE LMNA UBE2T GUCA1B IFT88 WDR11 PRPF4 FEZF1 PRPF3 TRIM32 BBS7 PDE8B FANCI EIF2S3 TP63 IER3IP1 ZNF408 FSHB SPRY4 CTDP1 PRKACA PTCH2 PRKAR1A STEAP3 ROM1 CAMKMT NR5A1 RP9 RP1 ELN RP2 RPGR ATM HAMP RERE CTNS CTNNB1 C8ORF37 LAS1L TOPORS KAT6B SUFU MAP2K1 IL17RD PRDM16 BBS12 RPE65 SNRNP200 SNRPN TBL2 SLX4 PRLR TP53 CYB5A SMAD4 BMP15 MGME1 PROP1 SEMA3E ZNF513 SOS1 SOS2
Hypogonadotrophic hypogonadism
Genes 120
HJV RAD51 SOX2 MKRN3 PCSK1 SOX3 PROK2 SNORD115-1 HFE KRAS RAF1 SOX9 SOX10 MAGEL2 LZTR1 SRA1 ZMPSTE24 NRAS LHX4 ANK1 RASA2 CLIP2 AXL RRM2B POLG DUSP6 HDAC8 WT1 IPW PWRN1 BAZ1B CDH23 POU1F1 SRY NDN CHD7 AIP PLXND1 RBM28 REV3L RRAS DCC RFC2 GPR101 PTCH1 GTF2IRD1 TYMP CCDC141 SNORD116-1 HESX1 FGF17 MAP3K1 POLR3A RNU4ATAC MKRN3-AS1 TFR2 MEN1 SIX6 RIT1 SEMA3A LHB DNAL4 LIMK1 GJB2 ANOS1 RAB3GAP1 PTPN11 OTX2 POLR3B GTF2I KISS1R NSMF PNPLA6 DHH LMNA BRAF PROKR2 WDR11 FEZF1 GLI2 TP63 HS6ST1 RAB3GAP2 FSHB SPRY4 A2ML1 NR0B1 CTDP1 NPAP1 DCAF17 PTCH2 RNF216 FGF8 NTN1 TAC3 FGFR1 NR5A1 ELN TACR3 FLRT3 PWAR1 CTNNB1 HERC2 HSD17B3 LAS1L DMRT1 KAT6B SUFU IL17RD KISS1 GNRH1 GNRHR SNRPN TBL2 PROP1 SEMA3E CBX2 PMM2 SOS1 SOS2