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Lactate Metabolism Study in HIV Infected Persons

Primary Purpose

HIV Infections, AIDS, Lactic Acidosis

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
cofactor supplementation (thiamine, riboflavin, L-carnitine)
Sponsored by
Queen's University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for HIV Infections focused on measuring HIV, HIV/AIDS, Lactic Acidosis, Supplementation, Lactate Clearance, Mitochondrial Toxicity, HAART

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Participants at least 18 years of age or older either: HIV negative, or HIV positive, not on antiretroviral therapy (for at least 6 months) or HIV positive, on D4T/ddC/ddI/AZT containing HAART or HIV positive, on D4T/ddC/ddI/AZT containing HAART, with hepatic steatosis/liver disease No evidence of acute illness on physical or laboratory examination Patients who have voluntarily consented to the study and signed the appropriate consent have not been supplementing with multi-vitamins, thiamine, riboflavin for at least 2 months prior to inclusion Exclusion Criteria: Active AIDS defining illness Treatment with growth hormone Known poor adherence with therapy End stage renal disease Pregnancy

Sites / Locations

  • Queen's University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

Arm Description

Individuals living with HIV who are naive to antiretroviral treatment, or who have been on a treatment interruption for at least six months

Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT

Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT and have liver disease.

HIV negative control group

Outcomes

Primary Outcome Measures

Changes in lactate clearance pre and post supplementation

Secondary Outcome Measures

to estimate the change in lactate metabolism and mitochondrial function after a change in antiretroviral therapy to a non D4t/ddC/ddI/AZT regime
Evidence of adverse response to supplements and/or antiretroviral medications

Full Information

First Posted
September 13, 2005
Last Updated
January 12, 2016
Sponsor
Queen's University
Collaborators
Ontario HIV Treatment Network
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1. Study Identification

Unique Protocol Identification Number
NCT00202228
Brief Title
Lactate Metabolism Study in HIV Infected Persons
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
July 2002 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Queen's University
Collaborators
Ontario HIV Treatment Network

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 PBMC's 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 D4T/ddI/ddC/AZT 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-D4T/ddI/ddC/AZT containing regime will demonstrate a decrease in lactate production from baseline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, AIDS, Lactic Acidosis, Lipodystrophy
Keywords
HIV, HIV/AIDS, Lactic Acidosis, Supplementation, Lactate Clearance, Mitochondrial Toxicity, HAART

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Individuals living with HIV who are naive to antiretroviral treatment, or who have been on a treatment interruption for at least six months
Arm Title
2
Arm Type
Experimental
Arm Description
Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT
Arm Title
3
Arm Type
Experimental
Arm Description
Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT and have liver disease.
Arm Title
4
Arm Type
Experimental
Arm Description
HIV negative control group
Intervention Type
Drug
Intervention Name(s)
cofactor supplementation (thiamine, riboflavin, L-carnitine)
Other Intervention Name(s)
L-carnitine: Carnitor
Intervention Description
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
Primary Outcome Measure Information:
Title
Changes in lactate clearance pre and post supplementation
Time Frame
two months
Secondary Outcome Measure Information:
Title
to estimate the change in lactate metabolism and mitochondrial function after a change in antiretroviral therapy to a non D4t/ddC/ddI/AZT regime
Time Frame
six months
Title
Evidence of adverse response to supplements and/or antiretroviral medications
Time Frame
two months (increased where necessary to cover any individual's entire study period should it exceed two months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participants at least 18 years of age or older either: HIV negative, or HIV positive, not on antiretroviral therapy (for at least 6 months) or HIV positive, on D4T/ddC/ddI/AZT containing HAART or HIV positive, on D4T/ddC/ddI/AZT containing HAART, with hepatic steatosis/liver disease No evidence of acute illness on physical or laboratory examination Patients who have voluntarily consented to the study and signed the appropriate consent have not been supplementing with multi-vitamins, thiamine, riboflavin for at least 2 months prior to inclusion Exclusion Criteria: Active AIDS defining illness Treatment with growth hormone Known poor adherence with therapy End stage renal disease Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wendy Wobeser, MD
Organizational Affiliation
Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen's University
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 3N6
Country
Canada

12. IPD Sharing Statement

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Lactate Metabolism Study in HIV Infected Persons

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