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Report for Clinical Trial NCT01589445

Developed by Shray Alag, 2020.
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

Metformin (002 group) Pioglitazone (001 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

Metformin (002 group) Pioglitazone (001 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 523
PDE6A IDH3A UBR1 IER3IP1 SPINK1 HNF1B PCARE ND1 OPA1 RP1 AGPAT2 TRNS1 MMP2 TTC8 PDX1 TGIF1 TREX1 CDON CFTR MKRN3 GCK INS PPARG HYMAI COX2 XRCC4 SNRNP200 NUBPL PTRH2 CEP19 NDUFB10 PROKR2 EYS LMNA TRNQ MAPK8IP1 LEPR TCF7L2 NSMCE2 PRPF4 ARL6 RDH12 ARL3 FGF8 GCK KDSR CEL DISP1 NR2E3 NDUFAF5 ARL2BP ERGIC1 PLAGL1 PRPF31 PNPLA6 NDUFV2 COX3 PRCD RLBP1 WFS1 KLF11 TRNL1 PDX1 NDUFA11 BLK KCNJ11 GPD2 SLC19A2 DHDDS MLXIPL LEP CLIP2 BMP2 BRCA2 TRNF IFT140 LMNA RP2 REEP6 NDUFS2 PDX1 PDE4D LIG4 RETN CNGA1 GLI2 NDP PNPLA2 EDA CYTB LHX1 PRSS1 NPM1 IFIH1 TBL2 ALMS1 GCK PRPH2 HAMP DCAF17 ABCC8 SNORD115-1 PRPF8 ENPP1 GUCA1B MEN1 MST1 NEUROD1 POMGNT1 HNF4A PTPN1 PPP1R3A FXN AIP KIAA1549 IGF2BP2 NKX2-5 EIF2S3 COX1 SLC29A3 ND5 SUFU CDKN2A HERC2 FXN CYP19A1 STAT3 MKKS SOX2 LIPC INSR GTF2I TDGF1 GCGR HMGA2 TWNK HFE TRNH HLA-DRB1 CORIN PRPF6 ZNF408 FGFR1 PROM1 FOS ZMPSTE24 PEX1 CPA1 HNF4A NPAP1 NDUFAF3 DLL1 BEST1 TRNK TRNL1 POLG CAV1 XRCC4 ND2 TUB CP SLC2A2 KRAS EFL1 NDUFS1 HNF1A SIX3 POLR3A RP9 TRNE AKT2 NODAL PPARG XRCC4 ND1 NDUFS4 GATA6 WRN DCAF17 TTC7A AKT2 RBP3 POC1A PAX4 RTEL1 NDUFA6 TRNS1 KCNJ11 INSR GJB3 INS CASR USP8 MAK FOXC2 FOXP3 HNF1B GATA3 IMPDH1 APOA5 LIPE TRNL1 LEMD3 IL6 PRKAR1A FGFR1 NDN COX1 FAM161A HESX1 INSR NRL NDUFS6 ABCC8 TRNC CFTR GJA1 PRKACA NDUFB9 TRNW COX3 TTPA GPR101 PLAGL1 TIMMDC1 GJA1 WRAP53 RNASEH2A HNF4A COX2 PAX4 FOXRED1 PAX4 DKC1 RRM2B SMAD4 BLK TMEM126B ND5 NDUFAF1 FLT1 KCNJ11 MAFA GATA6 IL2RA CLCNKB NDUFAF2 CTRC PPARG OFD1 IFT172 SPINK1 PRKAR1A RPGR ATM SNORD116-1 OTX2 NDUFA1 ZFYVE26 NDUFB3 BAZ1B PRSS2 BSCL2 ABCC8 INS WFS1 IFT88 PDE6B GAS1 ABCC8 ABCC8 RGR PALLD ND4 STOX1 GNAS NEK2 RFC2 CA4 HYMAI CTRC LIPE RHO MMP14 SCAPER NOP10 ITPR3 GCK SLC19A2 NHP2 HNF1B CRB1 PEX6 TWNK TRNQ NEUROD1 GTF2IRD1 ABCC8 ND6 DNAJC3 POLD1 GJB4 SPINK1 PARN BSCL2 VANGL1 SLC29A3 PDE11A PTPN22 PTF1A BRAF AHR PWRN1 HYMAI TRNV GLRX5 USB1 HLA-DQB1 ITCH SBDS TRNK GPR35 PRSS2 PROK2 STAT1 NSMCE2 CTNS PIK3R1 NDUFAF4 CDHR1 ZFP57 ATP6 TRNW PTF1A CTNNB1 AIP EIF2AK3 POLA1 GCK TRNE ELN NEUROG3 CISD2 GLIS3 DNAJC21 CAVIN1 ELMO2 PTCH1 ROM1 ZFP57 BBS2 LEPR LRP6 KCNJ11 PRKACA PRPF3 SLC25A4 DNM1L GCK HJV LRAT WFS1 HNF1B TP53 PNPLA2 ELN IRS2 NDUFV1 ND6 PRSS1 CERKL CLRN1 PPARG BBS2 MOG TOPORS ARNT2 FOXH1 RAC1 HNF4A PLIN1 TP53 TRNF NDUFB11 EIF2AK3 CFTR SNRPN USH2A KCNJ11 HNF1A STAT3 C8ORF37 APOE FUZ LMNB2 IGF1R TRNS2 LMNA IPW POLG2 PDX1 TERC SLC16A2 INS CAV1 NDUFS7 AR LMNA HGSNAT KLF11 SEMA4A FOXP3 CIDEC CTC1 PLIN1 IDH3B PCNT PEX10 GCK SPINK1 APPL1 HNF1A ZIC2 ABCA4 FBN1 ZNF513 TRNS2 CRX STUB1 NEUROD1 KLHL7 CISD2 PSTPIP1 ALMS1 LMNA PDX1 LIMK1 HNF1A RPE65 BRCA1 RNASEH2B CCDC28B STAT1 AHI1 AIRE ARMC5 NDUFS3 AGBL5 PDE4D TULP1 SHH DHX38 IL2RA HMGA1 CEL NDUFS8 ATM DNAJC3 INS MAGEL2 HNF1A EDA2R HFE MKRN3-AS1 SLC12A3 SLC30A8 UBR1 ND1 IMPG2 KCNJ11 PWAR1 CNOT1 ADAR BLM PDE8B PDX1 HNF4A IRS1 RNASEH2C INSR PIK3R1 CDH23 BBS1 TCF4 ZMPSTE24 ZBTB20 KIZ TINF2 KCTD1 WFS1 SRP54 APPL1 ND3 WFS1 PRSS1 SPATA7 AGPAT2 HBB MERTK WRN KCNJ11 PALB2 HNF1A LMNA PAX4 SARS2 SLC7A14 SOX3 MC4R PDE6G LMNA ARHGEF18 SAG AMACR MTNR1B CP CNBP PLCD1 CTRC FSCN2 TERT SAMHD1 CNGB1
Type II diabetes mellitus
Genes 182
SNRPN USH2A PDE6A IDH3A LIPC SNORD116-1 GTF2I GCGR C8ORF37 BAZ1B PCARE TRNH RP1 PRPF6 LMNA IPW IFT88 PDE6B ZNF408 ABCC8 RGR TTC8 PROM1 PDX1 AR ND4 NPAP1 HGSNAT NEK2 RFC2 CA4 KLF11 SEMA4A BEST1 TRNL1 RHO IDH3B MKRN3 SCAPER PPARG PCNT PEX10 TUB XRCC4 SNRNP200 SLC2A2 CEP19 CRB1 ABCA4 EYS MAPK8IP1 TRNQ TCF7L2 POLR3A RP9 GTF2IRD1 TRNE FBN1 PRPF4 AKT2 ZNF513 ARL6 TRNS2 RDH12 CRX STUB1 ARL3 NEUROD1 KLHL7 RBP3 SPINK1 NR2E3 ALMS1 TRNS1 KCNJ11 LIMK1 INSR HNF1A ARL2BP BRAF RPE65 AHR PWRN1 GLRX5 PRPF31 MAK PNPLA6 PRCD RLBP1 HNF1B AHI1 IMPDH1 TRNK AGBL5 TRNL1 TULP1 DHX38 GPD2 HMGA1 ATM NDN COX1 FAM161A NRL DHDDS CDHR1 MAGEL2 MKRN3-AS1 CLIP2 CTNNB1 AIP TRNF SLC12A3 IFT140 SLC30A8 RP2 POLA1 ND1 REEP6 IMPG2 ELN PWAR1 LIG4 RETN BLM PDX1 CNGA1 TRNW COX3 IRS1 INSR ROM1 BBS2 PRPF3 GCK KIZ TBL2 COX2 WFS1 GCK PRPH2 LRAT ABCC8 SNORD115-1 PRPF8 SPATA7 ENPP1 GUCA1B MEN1 IRS2 MERTK POMGNT1 HNF4A WRN ND6 HNF1A PTPN1 PPP1R3A CERKL CLRN1 PAX4 SLC7A14 KIAA1549 MC4R IGF2BP2 PDE6G ARHGEF18 SAG MOG AMACR TOPORS MTNR1B CLCNKB ND5 PLCD1 OFD1 FSCN2 IFT172 HERC2 CYP19A1 RPGR CNGB1