Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00023218
Status:
WITHDRAWN
Last Update Posted:
2015-03-09
First Post:
2001-08-29
Brief Title:
Effect of a Change in HIV Therapy on Liver Steatosis Inflammation and Fibrosis
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
Effect of Change to a Nucleoside Reverse Transcriptase Inhibitor NRTI-Sparing Regimen of Efavirenz EFV and LopinavirRitonavir LPVr on Liver Histology in HIV-1-Infected Individuals With Lactic Acidemia and Persistent Alanine Aminotransferase ALT Elevations on NRTI-Containing Antiretroviral Therapy
Status:
WITHDRAWN
Status Verified Date:
2003-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to look at how 2 different anti-HIV drug treatments affect the liver
The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors NRTIs may be linked to liver problems like fatty changes scarring abnormal liver function tests LFTs and lactic acidemia an increase in lactic acid in the blood Increased liver enzymes may mean liver damage The way that the liver changes in people with abnormal LFTs and lactic acidemia is not completely understood
The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors NRTIs may be linked to liver problems like fatty changes scarring abnormal liver function tests LFTs and lactic acidemia an increase in lactic acid in the blood Increased liver enzymes may mean liver damage The way that the liver changes in people with abnormal LFTs and lactic acidemia is not completely understood
Detailed Description:
This study provides a unique opportunity to prospectively assess the relationship of lactic acidemia with liver dysfunction and to determine whether lactic acidemia and liver dysfunction are likely to be secondary to NRTI-induced mitochondrial toxicity If lactic acidemia and hepatic fatty infiltration steatosis in this study population are secondary to NRTI-induced mitochondrial toxicity withdrawal of NRTI medications can be expected to result in partial improvement or resolution of these findings Furthermore this study will examine the possible additive ill effects of NRTI-induced mitochondrial toxicity on liver function in individuals coinfected with hepatitis C
This study is designed both as a stand-alone ACTG protocol providing an NRTI-sparing regimen and as a study coenrollable simultaneously with A5116
Patients enrolling in A5133 as a stand-alone study Patients on NRTI-containing regimens with elevated lactates and ALTs are enrolled into a single open-label NRTI-sparing treatment regimen of efavirenz EFV plus lopinavirritonavir LPVr which are provided by the study These patients follow virologic failuretoxicity management guidelines as detailed in the protocol
Patients coenrolling in A5116 Patients are studied on their assigned A5116 antiretroviral regimens with medication as provided by A5116 Those randomized in A5116 to the NRTI-sparing regimen of EFV and LPVr identical to that offered by A5133 will be assessed together with patients who entered A5133 as a stand-alone study Individuals assigned in A5116 to the continued NRTI arm of 2NRTIs plus EFV are enrolled into a separate observational arm of A5133 The impact of continued NRTI therapy on liver histology is assessed in this observational arm Virologic failuretoxicity management is in accordance with the A5116 protocol The definition of virologic failure in A5116 is identical to the definition used in A5133
Arm 1 consists of patients assigned to an NRTI-sparing regimen without evidence of HCV coinfection
Arm 2 consists of patients assigned to an NRTI-sparing regimen with evidence of HCV coinfection
Arm 3 consists of patients coenrolled in the NRTI-containing arm of A5116 with or without evidence of HCV coinfection
All patients are evaluated for safety and for virologic and immunologic responses In addition individuals undergo liver biopsy and upper abdominal CT scans within 30 days prior to entry and within 30 days prior to week 24 The biopsied tissue is reviewed for evidence of fatty infiltration inflammation and fibrosis The CT scans are assessed for degree of fatty infiltration If sufficient liver tissue is available the biopsied tissue will be assessed for other parameters Plasma PBMCs and sera are collected to explore the role of oxidative stress and other parameters in the development of hepatic fatty infiltration steatosis and hyperlactatemia The effect of changes in liver fatty infiltration and plasma lactate on lipoproteins will be explored Finally PBMC mtDNA content will be correlated with liver mtDNA content
This study is designed both as a stand-alone ACTG protocol providing an NRTI-sparing regimen and as a study coenrollable simultaneously with A5116
Patients enrolling in A5133 as a stand-alone study Patients on NRTI-containing regimens with elevated lactates and ALTs are enrolled into a single open-label NRTI-sparing treatment regimen of efavirenz EFV plus lopinavirritonavir LPVr which are provided by the study These patients follow virologic failuretoxicity management guidelines as detailed in the protocol
Patients coenrolling in A5116 Patients are studied on their assigned A5116 antiretroviral regimens with medication as provided by A5116 Those randomized in A5116 to the NRTI-sparing regimen of EFV and LPVr identical to that offered by A5133 will be assessed together with patients who entered A5133 as a stand-alone study Individuals assigned in A5116 to the continued NRTI arm of 2NRTIs plus EFV are enrolled into a separate observational arm of A5133 The impact of continued NRTI therapy on liver histology is assessed in this observational arm Virologic failuretoxicity management is in accordance with the A5116 protocol The definition of virologic failure in A5116 is identical to the definition used in A5133
Arm 1 consists of patients assigned to an NRTI-sparing regimen without evidence of HCV coinfection
Arm 2 consists of patients assigned to an NRTI-sparing regimen with evidence of HCV coinfection
Arm 3 consists of patients coenrolled in the NRTI-containing arm of A5116 with or without evidence of HCV coinfection
All patients are evaluated for safety and for virologic and immunologic responses In addition individuals undergo liver biopsy and upper abdominal CT scans within 30 days prior to entry and within 30 days prior to week 24 The biopsied tissue is reviewed for evidence of fatty infiltration inflammation and fibrosis The CT scans are assessed for degree of fatty infiltration If sufficient liver tissue is available the biopsied tissue will be assessed for other parameters Plasma PBMCs and sera are collected to explore the role of oxidative stress and other parameters in the development of hepatic fatty infiltration steatosis and hyperlactatemia The effect of changes in liver fatty infiltration and plasma lactate on lipoproteins will be explored Finally PBMC mtDNA content will be correlated with liver mtDNA content
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AACTG A5133 | None | None | None |