SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00062764

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Long-Term Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...

NCT00062764 Hepatitis
MeSH: Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis Hepatitis

1 Interventions

Name: Actos (Pioglitazone)

Description: Pts receive drug in a dose of 15 mg daily for at least 1 year; the dose is escalated to 30 mg daily if serum ALT levels do not fall to normal by the 1 year pt; if pts have a biochemical response, drug is continued for 3 years,

Type: Drug

Pioglitazone


Primary Outcomes

Description: A histological response was defined as a reduction in the NASH activity index by 3 points or more with improvements of at least 1 point each in steatosis, parenchymal inflammation, and hepatocellular injury.

Measure: Number of Patients With Improvement in Liver Histology

Time: 48 weeks

Secondary Outcomes

Measure: Number of Patients With Impaired Glucose Tolerance After Treatment

Time: 48 weeks

Measure: Mean Increase of Insulin Sensitivity Index

Time: 48 weeks

Measure: Average Increase in Weight After Treatment

Time: 48 weeks

Measure: Mean BMI Change

Time: 48 weeks

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 C282Y

Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---


2 H63D

Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---



HPO Nodes


HPO:
Hepatic steatosis
Genes 102
GABRD GPD1 HFE MPV17 LDLRAP1 TRAPPC11 HNF1B PNPLA2 ATP6AP1 ATP7B ZMPSTE24 ACADL ACADM ACADVL EARS2 LYRM4 DNAJC19 CYP7A1 MARS IARS ACAD9 POLD1 FOS ACOX1 RRM2B CYP19A1 POLG MRPL44 VPS33A AGPAT2 ETFA ETFB TMEM199 ETFDH LARS KCNAB2 FARSB COX15 APOB LMNB2 CAV1 MCCC1 APOE PPARG CPT1A XRCC4 TARS2 CPT2 SKI NSMCE2 TYMP HNF4A BCS1L HNRNPA1 CBS TFAM HNRNPA2B1 LDLR SLC40A1 COA8 DDOST PGM1 POLR3A ADK TRMU MRPS7 LRPPRC LIPA LIPE ABHD5 FBP1 NDUFAF1 LMNA ALMS1 CLPB COG6 DGUOK CIDEC SLC25A13 SAR1B SLC22A5 AKT2 CAVIN1 BSCL2 HADHA HADHB RERE HADH RMND1 HSD17B4 PLIN1 CARS2 ALDOB PRDM16 ABCG5 PCK1 ABCG8 PCK2 VCP PCSK9 CEP19 PMM2
Hepatitis
Genes 74
TTC7A MST1 TRAF3IP2 TPP2 TBX19 IL12A MET IL12RB1 RASGRP1 TCF4 HSD3B7 KRT8 SERPINA1 TCF3 VIPAS39 ATP7A IGF2R MMEL1 ATP7B ALMS1 SPIB KRT18 VPS33B CIITA PDGFRL PIK3CA GPR35 CYP7A1 GUSB PIK3R1 AMACR RFXANK SHPK IGHM PIEZO1 SLC25A15 BTK IL21R CD40LG BLNK GLIS3 APC CLEC7A AIRE LRRC8A CASP8 POU2AF1 XIAP CASP10 C1S CYP7B1 PRKCD CD79A CD79B IRF5 C4B IL17RC IL17RA IGLL1 CTNNB1 FAS SKIV2L FASLG SH2D1A RFX5 IL17F RFXAP TNFSF15 TNPO3 PGM1 STAT1 TP53 AXIN1 FOXP3