Trial record 1 of 173 for:    Lactic Acid Metabolism
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Lactate Metabolism Study in HIV Infected Persons

This study has been completed.
Sponsor:
Collaborator:
Ontario HIV Treatment Network
Information provided by (Responsible Party):
Wendy Wobeser, Queen's University
ClinicalTrials.gov Identifier:
NCT00202228
First received: September 13, 2005
Last updated: October 4, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
HIV Infections
AIDS
Lactic Acidosis
Lipodystrophy
Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
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.

Resource links provided by NLM:


Further study details as provided by Queen's University:

Primary Outcome Measures:
  • Changes in lactate clearance pre and post supplementation [ Time Frame: two months ] [ Designated as safety issue: No ]

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 [ Time Frame: six months ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: July 2002
Study Completion Date: September 2011
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Individuals living with HIV who are naive to antiretroviral treatment, or who have been on a treatment interruption for at least six months
Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
Other Name: L-carnitine: Carnitor
Experimental: 2
Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT
Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
Other Name: L-carnitine: Carnitor
Experimental: 3
Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT and have liver disease.
Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
Other Name: L-carnitine: Carnitor
Experimental: 4
HIV negative control group
Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
Other Name: L-carnitine: Carnitor

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00202228

Locations
Canada, Ontario
Queen's University
Kingston, Ontario, Canada, K7L 3N6
Sponsors and Collaborators
Queen's University
Ontario HIV Treatment Network
Investigators
Principal Investigator: Wendy Wobeser, MD Queen's University
  More Information

No publications provided

Responsible Party: Wendy Wobeser, Doctor, Queen's University
ClinicalTrials.gov Identifier: NCT00202228     History of Changes
Other Study ID Numbers: DMED-629-02
Study First Received: September 13, 2005
Last Updated: October 4, 2011
Health Authority: Canada: Ethics Review Committee

Keywords provided by Queen's University:
HIV
HIV/AIDS
Lactic Acidosis
Supplementation
Lactate Clearance
Mitochondrial Toxicity
HAART

Additional relevant MeSH terms:
Acidosis, Lactic
Acid-Base Imbalance
Metabolic Diseases
Skin Diseases, Metabolic
Lipid Metabolism Disorders
Acidosis
Acquired Immunodeficiency Syndrome
HIV Infections
Lipodystrophy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Skin Diseases
Carnitine
Riboflavin
Thiamine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 23, 2014