SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01589445

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.

- The present study was undertaken to assess the efficacy and safety of two different insulin sensitizers (namely Pioglitazone and Metformin) among subjects with type 2 diabetes mellitus (T2DM) in Bangladesh. - A prospective, double-blind, single group, 'within-subject' designed clinical trial of 77 diagnosed T2DM patients out of 130 patients with glycosylated haemoglobin (HbA1c) ≥7.2±1.5%, aged 46±6.4 years and registered for diabetes treatment in Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM) was carried out. - The study was conducted between November 2008 and September 2010. - Baseline data, included case history of the patients,anthropometric measurement, biomedical parameters psychosocial factors, were collected from each subject and then enrolled to receive treatment with 001 drug once daily for three months, then the patients were left for wash out with metformin 850mg once daily for one month; then they received 002 drug once daily for further three months. - Dietary chart was remained as before. - DNA was isolated by Chelex method using the primers and control DNA,restriction Digestion Enzyme Endonuclease Hae 111 for genotyping PPARγ-(Peroxisome Proliferator Activated Receptor gamma)Pro12Pro - (Proline12Proline)/Pro12Ala-(Proline12 Alanine))/Ala12Ala-(Alanine12Alanine). - The blinded drugs were decoded after analyzing results, 001 tablet was pioglitazone (30 mg once daily) and 002 tablets was metformin (850mg once daily). Bio-medical outcomes were measured to assess the efficacy of both the drugs each month. After finishing the treatment period the effects of two drugs were compared using SPSS.And the association between the pioglitazone drug effects and genetic polymorphism was also assessed. - The metformin effects was assessed also using the response rate of HbA1c <7.0% after 3 months treatment to the patients.

NCT01589445 Type 2 Diabetes Mellitus
MeSH: Diabetes Mellitus Diabetes Mellitus, Type 2
HPO: Diabetes mellitus Type II diabetes mellitus

2 Interventions

Name: Pioglitazone hydrochloride

Description: 77 patients were treated with pioglitazone hydrochloride (B001) for 3 months.Biomedical parameters were measured each month.

Type: Drug

Pioglitazone (001 group) Metformin (002 group)

Name: Metformin hydrochloride

Description: After the treatment with pioglitazone(001) for 3 months first and then patients were on one month washout period;in the washout period they were given metformin tablet 850mg once daily,then treated with 002 (metformin) for further 3 months. The same biomedical measurements were assayed.

Type: Drug

Pioglitazone (001 group) Metformin (002 group)


Primary Outcomes

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostasis Model Assessment Insulin Resistance(HOMA IR) Analysis 2: Quantitative Insulin sensitivity Check Index(QUICKI)

Measure: Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostatic Model Assessment of Beta cell function(HOMA percent B) Analysis 2: Homeostatic Model Assessment of Insulin Sensitivity (Homa percent S)

Measure: Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin

Time: 3 months for each drug

Secondary Outcomes

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1:Total Cholesterol(TC) Analysis 2:Triglyceride(TG) Analysis 3:High Density Lipoprotein(HDL) Analysis 4:Low Density Lipoprotein(LDL)

Measure: Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin

Time: 3 months for each drug

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 P12A

- DNA was isolated by Chelex method using the primers and control DNA,restriction Digestion Enzyme Endonuclease Hae 111 for genotyping PPARγ-(Peroxisome Proliferator Activated Receptor gamma)Pro12Pro - (Proline12Proline)/Pro12Ala-(Proline12 Alanine))/Ala12Ala-(Alanine12Alanine). - The blinded drugs were decoded after analyzing results, 001 tablet was pioglitazone (30 mg once daily) and 002 tablets was metformin (850mg once daily). --- Pro12Ala ---

We used a published document to select the primers for genotyping PPARγ Pro12Ala/Pro12Pro. --- Pro12Ala ---

The primers for the Pro12Ala SNP genotype, we amplified exon B using the reverse primer 5' CTG GAA GAC AAA CTA CAA GAG 3' and the forward primer 5' ACT CTG GGA GAT TCT CCT ATT GGC 3'. --- Pro12Ala ---

III.Control DNA: Professor Colin Palmer Laboratory, Biomedical Research Institute ,University of Dundee Medical School, University of Dundee, Scotland, UK sent six control samples of 3 types control DNA genotyped for PPARG SNP rs 1801282 (Pro12Ala). --- Pro12Ala ---

5) List of Abbreviations AEs Adverse Events ALT Alanine aminotransferase BMI Body Mass Index BMRC Bangladesh Medical Research Council BIRDEM Bangladesh Institute of Research and Rehabilitation in Diabetes,Endocrine and Metabolic Disorder BP Blood Pressure DNA Deoxynucleic Acid DBP Diastolic Blood Pressure DM Diabetes Mellitus EASD European Association for the Study of Diabetes EDTA Ethylene Diamine Tetra Acetic acid ELISA Enzyme Linked Immunosorbent Assay FBG/FSG Fasting Blood Glucose/Fasting Serum Glucose FSI Fasting Serum Insulin 2hBG 2 hours Blood Glucose HbA1c Glycosylated Haemoglobin HOMA percent B Homeostasis Model Assessment percentage of beta cell function HOMA percent S Homeostasis Model Assessment percentage of sensitivity HOMA IR Homeostasis Model Assessment Insulin Resistance HDL-C High Density Lipid Cholesterol IU/L International Unit/Litre LDL-C Low Density Lipid Cholesterol ml millilitre mm millimetre mg/dl milligram/ decilitre MLR Multiple Logistic Regression OPD Outdoor Patient Department OMIM Online Mendelian Inheritance in Man OR Odds Ratio PPARγ Peroxisome Proliferator Activated Receptor gamma Pro12Pro Proline12Proline Pro12Ala Proline 12 Alanine Ala12Ala Alanine12Alanine PCR Polymerase Chain Reaction QUICKI Quantitative Insulin sensitivity Check Index SD Standard Deviation SPSS Statistical Package for Social Science SBP Systolic Blood Pressure TC Total Cholesterol TG Triglyceride T2DM Type 2 Diabetes Mellitus TZD Thiazolidinedione µl Microliter WHO World Health Organization --- Pro12Ala ---



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