HIV InfectionsPhase 4NCT00202228
Lactate Metabolism Study in HIV Infected Persons
A Phase 4 study testing cofactor supplementation (thiamine, riboflavin, L-carnitine) in people with HIV Infections and AIDS, run by Queen's University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, AIDS, Lactic Acidosis
- What is being tested?
- cofactor supplementation (thiamine, riboflavin, L-carnitine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2002to Sep 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Active AIDS defining illness
- Treatment with growth hormone
- Known poor adherence with therapy
- End stage renal disease
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- HIV Infections, AIDS, Lactic Acidosis, Lipodystrophy
- Being tested
- cofactor supplementation (thiamine, riboflavin, L-carnitine)
- Keywords
- HIV, HIV/AIDS, Lactic Acidosis, Supplementation, Lactate Clearance, Mitochondrial Toxicity, HAART
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome, Acidosis, Lactic, Lipodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cofactor supplementation (thiamine, riboflavin, L-carnitine)Drug
Also called L-carnitine: Carnitor
Thiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Individuals living with HIV who are naive to antiretroviral treatment, or who have been on a treatment interruption for at least six months Receives: Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine) |
| 2 | Experimental | Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT Receives: Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine) |
| 3 | Experimental | Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT and have liver disease. Receives: Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine) |
| 4 | Experimental | HIV negative control group Receives: Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in lactate clearance pre and post supplementation
Measured: two months
Secondary outcomes (2)
to estimate the change in lactate metabolism and mitochondrial function after a change in antiretroviral therapy to a non D4t/ddC/ddI/AZT regime
Measured: six months
Evidence of adverse response to supplements and/or antiretroviral medications
Measured: two months (increased where necessary to cover any individual's entire study period should it exceed two months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJul 2002
- Primary completionOct 2008
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario HIV Treatment Network
- Responsible party
- Principal investigator, Dr. Wendy Wobeser, Queen's University
- Investigators
- Wendy Wobeser, MD, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202228
- Sponsor's protocol ID
- DMED-629-02
- Status last verified
- Jan 2016
- First submitted
- 13 Sep 2005
- Last updated
- 13 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00202228
- Acronym / sponsor ID
- DMED-629-02
- Conditions
- HIV Infections, AIDS, Lactic Acidosis, Lipodystrophy
- Keywords
- HIV, HIV/AIDS, Lactic Acidosis, Supplementation, Lactate Clearance, Mitochondrial Toxicity, HAART
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Collaborators
- Ontario HIV Treatment Network
- Study start
- Jul 2002
- Primary completion
- Oct 2008 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)Individuals living with HIV who are naive to antiretroviral treatment, or who have been on a treatment interruption for at least six months |
| 2 | Experimental | Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT |
| 3 | Experimental | Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)Individuals living with HIV who are on an antiretroviral regimen including one of D4T/ddI/ddC/AZT and have liver disease. |
| 4 | Experimental | Drug: cofactor supplementation (thiamine, riboflavin, L-carnitine)HIV negative control group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participants at least 18 years of age or older either:
- 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
Key exclusion criteria (5 listed)
- Active AIDS defining illness
- Treatment with growth hormone
- Known poor adherence with therapy
- End stage renal disease
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cofactor supplementation (thiamine, riboflavin, L-carnitine)Also: L-carnitine: CarnitorThiamine: 50 mg po od; Riboflavin: 100 mg po od; L-carnitine: 990 mg po bid. | Drug | 1, 2, 3, 4 |
Primary outcome
Changes in lactate clearance pre and post supplementation
Time frame: two months
2 secondary outcomes
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
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wendy Wobeser, MD principal investigator
Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cofactor supplementation (thiamine, riboflavin, L-carnitine) in people with HIV Infections and AIDS, run by Queen's University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in lactate clearance pre and post supplementation (time frame: two months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2016.