SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03705195

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Study of Sulphonylurea Synergy With Incretins

The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy. All participants will undergo two matched clamps. The first matched clamp will be with no intervention. The second intervention matched clamp, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will participate in the dose-ranging phase. They will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve participants will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response.

NCT03705195 Type 2 Diabetes Mellitus
MeSH: Diabetes Mellitus Diabetes Mellitus, Type 2
HPO: Diabetes mellitus Type II diabetes mellitus

1 Interventions

Name: Gliclazide

Description: Low dose liquid gliclazide will be used with the second matched clamp (OGTT/IGII) in visits 4 & 5.

Type: Drug

Low Dose Gliclazide


Primary Outcomes

Description: Comparison of two matched clamps (oral glucose tolerance test + isoglycaemic intravenous glucose infusion). Matched clamp 1 - control. Matched clamp 2 - low dose gliclazide. Levels of insulin/c-peptide, incretin hormones and plasma glucose will be compared in the presence and absence of low dose gliclazide

Measure: Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide)

Time: Through four study visits completed over 4 weeks

Secondary Outcomes

Description: Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in matched clamp(gliclazide). Differences will then be compared by participants genotype e.g. insulin secretory response for E23K, E23E, K23K variants.

Measure: Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K)

Time: Through four study visits completed over 4 weeks

Purpose: Basic Science

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 E23K

Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K). --- E23K ---

insulin secretory response for E23K, E23E, K23K variants.. Inclusion Criteria: - Age 40 - 80, - Age of Diabetes Diagnoses ≥ 35 - T2DM on no treatment or metformin monotherapy - White British - HbA1c ≤ 8% (64mmol/mol) - eGFR ≥ 50ml/min-1 - ALT ≤ 2.5 x ULN - Able to consent Exclusion Criteria: - Type 1 Diabetes Mellitus - HbA1c > 8.0% (> 64mmol/mol) - eGFR <50ml/min-1 - ALT >2.5 x ULN - Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men) - Pregnancy, lactation or a female planning to conceive within the study period - Established pancreatic disease - Participating in clinical phase of another interventional trial/study or have done so within the last 30 days - Any other significant medical reason for exclusion as determined by the investigator Inclusion Criteria: - Age 40 - 80, - Age of Diabetes Diagnoses ≥ 35 - T2DM on no treatment or metformin monotherapy - White British - HbA1c ≤ 8% (64mmol/mol) - eGFR ≥ 50ml/min-1 - ALT ≤ 2.5 x ULN - Able to consent Exclusion Criteria: - Type 1 Diabetes Mellitus - HbA1c > 8.0% (> 64mmol/mol) - eGFR <50ml/min-1 - ALT >2.5 x ULN - Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men) - Pregnancy, lactation or a female planning to conceive within the study period - Established pancreatic disease - Participating in clinical phase of another interventional trial/study or have done so within the last 30 days - Any other significant medical reason for exclusion as determined by the investigator Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. --- 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