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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
Group Labels: 2

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
Group Labels: 2

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:
HP:0000819: Diabetes mellitus
Genes 530
IL2RA HGSNAT ABCC8 RP1 APPL1 ND5 TCF4 GPR101 TRNS2 INSR IER3IP1 TWNK RRM2B HYMAI MAK BSCL2 IFT172 SPINK1 BEST1 XRCC4 HNF1B FSCN2 CTRC PWRN1 TRNL1 KCNJ11 ATM STOX1 ABCC8 ENPP1 CRX COX3 BBS2 CRB1 IGF1R PRKACA TINF2 FOXP3 KCNJ11 TRNS1 IRS2 MAFA HNF1B RP9 PDE4D MST1 TRNL1 WFS1 LMNB2 KLF11 GLIS3 SUFU PDE4D ATP6 DNAJC21 PRPF4 KCTD1 ND1 TUB CYTB RHO INS HBB NDUFS1 CLCNKB ZFYVE26 HFE COX2 CTRC INS GCK EIF2AK3 SAG KRAS GLI2 PALB2 CORIN USH2A NHP2 BSCL2 PRPF6 FGF8 PDX1 LIPE RNASEH2A CNGA1 TDGF1 MERTK AEBP1 PDE11A CP PPP1R3A FOS ARHGEF18 PLCD1 SLC29A3 IDH3B LMNA ND1 TRNQ PRPF3 SLC7A14 NDP XRCC4 PAX4 PDX1 MAPK8IP1 ND3 SNORD116-1 SLC2A2 IPW PTF1A INS CEL PAX4 PTF1A LIG4 HMGA2 HMGA1 NDUFS2 TRNS1 RETN POLD1 PPARG ALMS1 PROK2 FGFR1 PCNT INS LRP6 CAT HNF1A CTNNB1 COX2 INSR POLG2 SCAPER PRCD PCARE HYMAI CFTR DHDDS ZIC2 SLC25A4 LEPR BLM GJA1 KCNJ11 ZNF513 FBN1 AKT2 MMP2 LEP ARMC5 CAV1 PTPN22 GUCA1B GCK GCK PDE8B LMNA NEUROG3 FXN GATA6 SLC16A2 SNORD115-1 PAX4 BMP2 TRNL1 AMACR PTPN1 RAC1 PPARG GJA1 FLT1 PNPLA2 ZFP57 BRCA2 STAT1 SLC30A8 SBDS PDX1 POC1A ROM1 C8ORF37 PDE6B DISP1 CTNS PDE6G COX1 ZMPSTE24 IRS1 GCK LIPE ELN ABCC8 FXN DKC1 RGR HNF1A ND5 SIX3 ND4 TREX1 PROM1 SEMA4A CNBP ARL6 MEN1 TRNQ CPA1 HNF1A CAV1 ABCA4 MAGEL2 ELN TULP1 COX1 REEP6 ABCC8 NDUFA11 PLIN1 NDUFAF2 GCK DHX38 WRN HLA-DRB1 GJB4 NDUFB9 FOXP3 LEMD3 PPARG FOXRED1 DLL1 NDUFS7 MMP14 RP2 WRN RLBP1 SARS2 WRAP53 EFL1 RFC2 SLC19A2 NDUFAF1 TERC CFTR ND6 CDKN2A LMNA SPINK1 STAT3 UBR1 CIDEC ND6 DNAJC3 PLIN1 WFS1 ZFP57 ATM STUB1 HNF1B ARL3 IFT88 BRCA1 CEL TRNC OFD1 TERT DCAF17 TRNF NODAL MKRN3-AS1 NDUFA6 PNPLA2 SPINK1 NDUFAF4 PIK3R1 RDH12 STAT3 ND2 ITCH HNF1A FOXC2 APPL1 IDH3A CASR CNOT1 EDA2R PLAGL1 CYP19A1 POMGNT1 INSR AGPAT2 SLC12A3 WFS1 CISD2 GLRX5 HNF4A IL6 LIMK1 LHX1 TBL2 INS BLK PNPLA6 USP8 SLC29A3 RNASEH2B ZMPSTE24 ARL2BP IMPG2 TWNK TRNF TGIF1 GATA3 ZBTB20 RBP3 KIZ SRP54 PRPF8 TOPORS PEX10 DNM1L GJB3 NDUFS4 DNAJC3 ITPR3 RPGR FUZ NDUFS3 SOX2 GATA6 HERC2 PEX1 TRNW PDX1 TKT FAM161A AR LEPR HNF1A NSMCE2 WFS1 IFIH1 ELMO2 ARNT2 TP53 CEP19 NDUFS6 BBS1 FGFR1 HYMAI NDUFAF3 CLIP2 NDUFV1 SLC19A2 INSR NR2E3 MKKS KIAA1549 TMEM126B CP PPP1R15B KLHL7 CNGB1 GCK GCGR PTRH2 MC4R ADAR APOA5 GAS1 TIMMDC1 STAT1 AGBL5 PARN EIF2AK3 SHH FOXH1 NDUFAF5 PROKR2 WFS1 CA4 KDSR SPINK1 HNF1A TRNK KCNJ11 USB1 PAX4 EYS NEK2 PRSS1 CERKL NDUFS8 ND1 LMNA TRNK MKRN3 ERGIC1 BRAF HNF1B MOG RTEL1 POLG CCDC28B CDH23 PEX6 TRNV NDN LMNA NDUFB10 PIK3R1 KCNJ11 ZNF408 HESX1 KCNJ11 UBR1 GNAS PRSS1 ALMS1 HBB BBS2 GCK CDHR1 PRPF31 SMAD4 AIP NEUROD1 HAMP NDUFB11 TTPA TRNE AKT2 ABCC8 DMXL2 GTF2I CTRC TRNW COX3 POLR3A MTNR1B IL2RA LRAT PRKAR1A KCNJ11 HNF4A PRPH2 RNASEH2C LMNA CLRN1 TRNH OPA1 NPM1 ABCC8 HFE NRL PDE6A APOE GPR35 HNF4A AIRE TRNS2 MLXIPL GPD2 LMNA TTC8 SAMHD1 EDA TP53 NUBPL SNRPN TRMT10A NKX2-5 PWAR1 RPE65 PDX1 IGF2BP2 PRSS2 PRKACA AHI1 CAVIN1 PTCH1 BLK PPARG SPATA7 NPAP1 EIF2S3 BAZ1B SNRNP200 HNF4A POLA1 AHR NEUROD1 NDUFV2 PDX1 PSTPIP1 HJV AIP PALLD HLA-DQB1 TRNE TCF7L2 CTC1 NSMCE2 TTC7A NOP10 OTX2 PRSS2 PRKAR1A XRCC4 SOX3 HNF4A IMPDH1 NDUFB3 IFT140 DCAF17 KLF11 NEUROD1 FOXP1 CDON LIPC PLAGL1 CISD2 NDUFA1 PRSS1 GTF2IRD1 VANGL1 AGPAT2