Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00202228
Status:
COMPLETED
Last Update Posted:
2016-01-13
First Post:
2005-09-13
Brief Title:
Lactate Metabolism Study in HIV Infected Persons
Sponsor:
Queens University
Organization:
Queens University
Study Overview
Official Title:
Lactic Acid Metabolism in HIV-Infected Persons Predicting Abnormalities in Lactate Production and Clearance Related to Treatment and Liver Disease and Measuring the Impact of Vitamin Supplementation
Status:
COMPLETED
Status Verified Date:
2016-01
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:
Lactic acidosis is a potentially life-threatening disease associated with the treatment of chronic HIV infection Although acidosis is rare hyperlactatemia is common and may have long term consequences yet to be recognized Lactic acidosis is a manifestation of mitochondrial toxicity consequences which have yet to be fully recognized and understood In this study we propose to look at lactate clearance and production by two methods in four treatment groups including HIV positive subjects on highly active antiretroviral therapy HAART treatment regimes and without HAART regimes with liver steatosis and without and compared with HIV negative controls Supplementation with cofactors thiamine niacin and L-carnitine which may have a positive effect on lactate metabolism by facilitating mitochondrial function will be studied as well
Detailed Description:
The management of chronic HIV infection is increasingly dependent upon the management of long term toxicities of therapy Toxicities are often metabolic and include hyperlipidemia hyperglycemia osteopenia and lipodystrophy While more rare lactic acidosis may present also and is associated with mortality The consequences of chronic hyperlactatemia are not well understood but it is known that the cause is likely related to mitochondrial toxicity of nucleoside analogues which are the cornerstone class of HIV therapies
No treatments for the syndrome of chronic lactic acidosis have been proven but evidence exists which suggests that the utilization of cofactors such as thiamine riboflavin and L-carnitine in the management of the acute syndrome these factors may alleviate the mitochondrial compromise
The mechanism underlying lactic acidemia may be a result of both increased production as a result of mitochondrial dysfunction and poor clearance of lactate by the liver which is the primary organ for clearance Some of this liver dysfunction could also be attributable to mitochondrial toxicity
In this study we propose to study lactate metabolism among persons with chronic HIV infection both on treatment and treatment naive and compare the results to uninfected control population We will also study a subset of HIV infected persons with known underlying liver disease Two methodologies will be used a lactate challenge test and a forearm ischemia test The effect of supplementation with cofactors which may have a positive effect on lactate metabolism by facilitating mitochondrial function will be studied as well All persons enrolled for evaluation will have these tests repeated 4-6 weeks after supplementation with standardized doses of cofactors thiamine and L-carnitine between tests Fat tissue samples and PBMCs will be collected and analyzed for quantity and function and participants will have liver ultrasounds Liver biopsies will be completed on those subjects where clinically indicated The results of the study will provide important insights into the effects on lactate metabolism nucleoside analogues and HIV itself
Our primary hypothesis is that persons on D4TddIddCAZT containing highly active antiretroviral therapy HAART will demonstrate increased lactate production compared to HIV negative controls that lactate metabolism will be normalized after treatment with cofactors riboflavin thiamine L-carnitine that persons with liver disease on therapy will demonstrate prolonged lactate clearance and that persons changed to a non-D4TddIddCAZT containing regime will demonstrate a decrease in lactate production from baseline
No treatments for the syndrome of chronic lactic acidosis have been proven but evidence exists which suggests that the utilization of cofactors such as thiamine riboflavin and L-carnitine in the management of the acute syndrome these factors may alleviate the mitochondrial compromise
The mechanism underlying lactic acidemia may be a result of both increased production as a result of mitochondrial dysfunction and poor clearance of lactate by the liver which is the primary organ for clearance Some of this liver dysfunction could also be attributable to mitochondrial toxicity
In this study we propose to study lactate metabolism among persons with chronic HIV infection both on treatment and treatment naive and compare the results to uninfected control population We will also study a subset of HIV infected persons with known underlying liver disease Two methodologies will be used a lactate challenge test and a forearm ischemia test The effect of supplementation with cofactors which may have a positive effect on lactate metabolism by facilitating mitochondrial function will be studied as well All persons enrolled for evaluation will have these tests repeated 4-6 weeks after supplementation with standardized doses of cofactors thiamine and L-carnitine between tests Fat tissue samples and PBMCs will be collected and analyzed for quantity and function and participants will have liver ultrasounds Liver biopsies will be completed on those subjects where clinically indicated The results of the study will provide important insights into the effects on lactate metabolism nucleoside analogues and HIV itself
Our primary hypothesis is that persons on D4TddIddCAZT containing highly active antiretroviral therapy HAART will demonstrate increased lactate production compared to HIV negative controls that lactate metabolism will be normalized after treatment with cofactors riboflavin thiamine L-carnitine that persons with liver disease on therapy will demonstrate prolonged lactate clearance and that persons changed to a non-D4TddIddCAZT containing regime will demonstrate a decrease in lactate production from baseline
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None