Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

Study Overview
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Brief Summary
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This is a randomized placebo-controlled trial to examine if once daily probiotic therapy will lower serum LPS levels and immune activation among HIV-infected youth.

Detailed Description
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This is a double masked randomized placebo-controlled trial to examine if once daily probiotic therapy will lower serum lipopolysaccharide (LPS) levels and immune activation among HIV-infected youth. The study will enroll two cohorts: (1) a cohort of subjects who are not receiving antiretroviral therapy (ART) and have absolute CD4 T-cell count greater than 350 cells/ul and quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml; and (2) a cohort of subjects who are receiving ART and have absolute CD4 T-cell count greater than 350 cells/ul and and quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml.

Official Title
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A Randomized Placebo-Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents

Conditions
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HIV Infection

Intervention / Treatment
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* Dietary Supplement: Probiotics
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be considered eligible for enrollment, an individual must meet the criteria listed below. Age 13 years and 0 days to 24 years and 364 days at the time of consent Confirmed or suspected to have acquired HIV infection at age 10 years or older HIV-1 infection as documented by any FDA-approved ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, HIV-1 DNA, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to pre-entry Absolute CD4 T-cell count greater than 350 cells/ul at pre-entry Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 50,000 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Quantitative HIV-1 plasma RNA (viral load) less than 400 copies/ml on two consecutive determinations at least 8 weeks apart in the 24 weeks prior to and including pre-entry Willingness to refrain from regular use of foods/supplements containing probiotics other than that supplied by the study during the course of study participation Exclusion Criteria: To be considered eligible for enrollment, an individual must not meet any of the criteria listed below. Known hypersensitivity to probiotics Active AIDS-defining condition or acute serious illness Cohort 1 - Not receiving ART and no exposure to ART in the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 50,000 copies/ml during the 24 weeks prior or at pre-entry. Cohort 2 - Currently receiving ART and received ART for at least the 24 weeks prior to pre-entry: Any quantitative HIV-1 plasma RNA (viral load) equal to or greater than 400 copies/ml during the 24 weeks prior or at pre-entry Known history of inflammatory bowel disease or similar disorder of the GI tract Current treatment with immune-modulating or immune-suppressive therapy Active malignancy at pre-entry Pregnancy Grade 3 or higher clinical or laboratory toxicities at the time of randomization Regular use of foods or supplements containing probiotics within the 2 weeks prior to randomization (see Appendix V) Concurrent participation in the ATN 061, 071, 081, and/or 101 protocols

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects randomized to the placebo arm. | Dietary Supplement: Placebo<br>* The placebo sticks will contain approximately 1 g maltodextrin<br>|
| Experimental: Probiotics<br>The probiotics use in the study contains two strains of Lactobacillus plantarum. Each dose of the active study agent contains contains 1 g maltodextrin plus the probiotic bacteria Lp299v (5 x 109 cfu) and Lp299 (5 x 109 cfu). | Dietary Supplement: Probiotics<br>* Probiotic is a live microorganism that when administered in adequate amounts confer a health benefit on the host. It is classified by the FDA as generally recognized as safe (GRAS)<br>* Other names: No other names.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma LPS levels | To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS. | 32 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool colonization with Lactobacillus plantarum | To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics. | 32 Weeks | 
| Plasma pro-inflammatory cytokines and macrophage activation | To determine if probiotic colonization of the gastrointestinal (GI) tract with Lactobacillus plantarum decreases levels of plasma pro-inflammatory cytokines and macrophage activation by measuring tumor necrosis factor alpha (TNFα), interferon alpha (IFNα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-12p70 (IL-12p70), interleukin-10 (IL-10), and soluble CD14 (sCD14) as well as other markers of microbial translocation. | 32 Weeks | 
| Lymphocyte activation markers | To determine if probiotic colonization of the GI tract with Lactobacillus plantarum results in decreased levels of T-cell activation markers as measured by shedding of soluble CD27 (sCD27), proportion of CD4 Th17 subsets, and expression of CD38 and HLA DR on CD8 T cells within ART treated and untreated HIV-infected youth. | 32 Weeks | 
| Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count | To examine if probiotics have any impact on quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count among the study cohort. | 32 Weeks | 
| Stool microbial composition and genetic diversity | To molecularly characterize changes in overall bacteria diversity within the stool specimens of youth treated with probiotics. | 32 Weeks | 
| Safety labs and adverse events as a measure of acceptability and tolerability of probiotics | To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth. | 32 Weeks | 
| Food frequency and probiotics and lifestyle questionnaires | To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels. | 32 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Probiotics