SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01762046

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans

The SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.

NCT01762046 Diabetes Mellitus, Type 2
MeSH: Diabetes Mellitus Diabetes Mellitus, Type 2
HPO: Diabetes mellitus Type II diabetes mellitus

3 Interventions

Name: Glipizide

Type: Drug

Glipizide and Metformin

Name: Metformin

Type: Drug

Glipizide and Metformin

Name: Oral Glucose Tolerance Test

Type: Other

Glipizide and Metformin


Primary Outcomes

Description: Investigators will measure insulin and glucose levels for 240 minutes after Glipizide administration on Visit 1, and compare them by genotype at selected loci.

Measure: Glipizide response

Time: Between 0-240 minutes, Visit 1

Description: Investigators will measure the change in glycemic measures between Visit 1 and Visit 2 as an index of Metformin response, and compare them by genotype at selected loci.

Measure: Metformin response

Time: 7 days

Secondary Outcomes

Description: Investigators will measure GLP-1 and GIP during the 120 minutes of Visit 2, and compare them by genotype at selected loci.

Measure: Incretin levels

Time: 120 minutes, Visit 2

Description: Investigators will measure proinsulin and glucagon levels at regular intervals during Visits 1 and 2, and compare them by genotype at selected loci.

Measure: Proinsulin, glucagon

Time: 7 days

Description: Investigators will perform metabolomic profiling of plasma samples at regular intervals in Visits 1 and 2, by using initially a targeted approach on an existing platform that measures ~400 metabolites (both polar and non-polar); they will compare their relative concentrations by genotype at selected loci before and after the interventions.

Measure: Metabolomics

Time: 7 days

Description: Investigators will measure 25-hydroxy vitamin D levels at baseline, and examine its effects on glycemic measures during Visits 1 and 2.

Measure: Vitamin D

Time: Baseline

Purpose: Basic Science

Single Group Assignment


There is one SNP

SNPs


1 E23K

In particular, sulfonylureas may have differential effects on individuals depending on the allelic variant they carry at KCNJ11 E23K; conversely, because TCF7L2 is postulated to influence insulin secretion by regulating the action of glucagon-like peptide 1 (GLP-1), and sulfonylureas act at a different step in the insulin secretion pathway, the effect of sulfonylureas on insulin secretion could be independent of genetic variation at TCF7L2. --- E23K ---



HPO Nodes


HPO:
Diabetes mellitus
Genes 326
SOX2 MKRN3 SOX3 MKKS SNORD115-1 SPATA7 CDKN2A HFE CERKL UBR1 PRPF31 LRAT PRSS1 TREX1 PRSS2 IFT140 ARL2BP GLRX5 SLC29A3 MAK AHI1 ABCA4 PDE4D ZBTB20 PDE6A PDE6G ZMPSTE24 IMPDH1 CEL STUB1 SPINK1 RTEL1 PDE6B LEMD3 INS HLA-DQB1 GJB4 IFT172 AMACR KIZ CDHR1 HLA-DRB1 CYP19A1 CFTR DHX38 MAFA GAS1 INSR ZFP57 MC4R GATA3 CTRC GATA6 PDX1 IPW PEX1 BBS1 PWRN1 PEX6 BBS2 DNAJC21 PEX10 CDH23 SRP54 DHDDS NDN PRPF6 GCK NDP KCTD1 AGBL5 GPR101 PTCH1 HNF4A ADAR TTPA TUB SNORD116-1 HESX1 STAT1 STAT3 TULP1 BLK BLM ARL6 IFIH1 TTC8 GJA1 PROM1 NEK2 GJB3 SAG FBN1 NEUROD1 SARS2 PNPLA6 BRCA1 ALMS1 BRAF BRCA2 PROKR2 CLCNKB TINF2 KLHL7 REEP6 FAM161A PIK3R1 GLI2 ABCC8 KCNJ11 RNASEH2C ARNT2 NPAP1 SCAPER FSCN2 DCAF17 AHR PRCD DKC1 FGF8 PLAGL1 AKT2 NOP10 FGFR1 PLCD1 GNAS PWAR1 SEMA4A HERC2 MERTK FOXH1 PLIN1 HYMAI NODAL USH2A CLRN1 CNGB1 CNGA1 EIF2AK3 MOG CDON CA4 IMPG2 PDE11A FOXP3 FOXC2 HJV PROK2 RNASEH2B KRAS TCF4 KLF11 EFL1 HNF1A BEST1 HNF1B PNPLA2 NR2E3 MAGEL2 POC1A OFD1 SLC25A4 USB1 NRL CLIP2 APOA5 CISD2 RNASEH2A CTC1 PTF1A WFS1 GPR35 POLD1 FOS RRM2B POLG AGPAT2 RBP3 WRN SLC19A2 HGSNAT GLIS3 SHH AIRE KIAA1549 FUZ BAZ1B RDH12 POMGNT1 PRPH2 ARHGEF18 DNM1L CP TWNK CPA1 CASR PCARE SAMHD1 TDGF1 AIP CAV1 PSTPIP1 FXN APOE IDH3B PPARG RFC2 XRCC4 WRAP53 SIX3 GTF2IRD1 NSMCE2 PRPF8 DLL1 NHP2 TERC TERT EDA RGR SLC7A14 AR LEP OPA1 LEPR PALB2 POLR3A RHO CRB1 ZIC2 MKRN3-AS1 CRX RLBP1 TTC7A PPP1R3A CNBP MST1 ERGIC1 LHX1 TGIF1 USP8 MLXIPL LIG4 LIMK1 EYS ARL3 LIPE OTX2 IGF1R GTF2I HMGA2 ATP6 TRNC SLC12A3 LMNA COX1 COX2 COX3 GUCA1B IFT88 CYTB SLC16A2 PRPF4 PRPF3 ELMO2 PDE8B VANGL1 SBDS EIF2S3 IER3IP1 ZNF408 CIDEC ND1 ARMC5 ND4 ND5 ND6 PRKACA PRKAR1A NKX2-5 APPL1 TRNE TRNF ROM1 ZFYVE26 PARN CAVIN1 BSCL2 TRNH RP9 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM HAMP CTNS CTNNB1 C8ORF37 TRNQ TRNS1 TRNS2 POLG2 TRNV TOPORS TRNW KDSR HBB SUFU IL2RA RPE65 DNAJC3 SNRNP200 SNRPN PALLD TBL2 DISP1 EDA2R NEUROG3 TP53 CEP19 SMAD4 PCNT ZNF513
Type II diabetes mellitus
Genes 152
MKRN3 SNORD115-1 SPATA7 CERKL PRPF31 LRAT KLF11 IFT140 HNF1A BEST1 HNF1B ARL2BP NR2E3 GLRX5 MAK AHI1 MAGEL2 ABCA4 PDE6A PDE6G IMPDH1 OFD1 STUB1 SPINK1 NRL CLIP2 PDE6B IFT172 AMACR KIZ CDHR1 CYP19A1 DHX38 INSR RBP3 WRN MC4R HGSNAT PDX1 IPW KIAA1549 PWRN1 BBS2 BAZ1B PEX10 RDH12 POMGNT1 PRPH2 DHDDS ARHGEF18 PCARE NDN PRPF6 GCK IDH3B AGBL5 RFC2 XRCC4 GTF2IRD1 PRPF8 RGR TUB SLC7A14 AR SNORD116-1 TULP1 POLR3A RHO CRB1 MKRN3-AS1 CRX BLM RLBP1 PPP1R3A ARL6 TTC8 PROM1 LIG4 NEK2 LIMK1 EYS ARL3 SAG FBN1 GTF2I PNPLA6 SLC12A3 LMNA COX1 ALMS1 BRAF COX2 COX3 GUCA1B CLCNKB IFT88 KLHL7 PRPF4 PRPF3 REEP6 FAM161A ABCC8 ZNF408 ND1 ND4 ND5 ND6 NPAP1 SCAPER FSCN2 AHR PRCD TRNE TRNF ROM1 AKT2 TRNH RP9 PLCD1 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM PWAR1 SEMA4A CTNNB1 C8ORF37 HERC2 TRNQ MERTK TRNS1 TRNS2 TOPORS TRNW USH2A RPE65 CLRN1 CNGB1 CNGA1 SNRNP200 SNRPN TBL2 MOG CEP19 CA4 IMPG2 PCNT ZNF513