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

Not Applicable

Withdrawn

• Conditions: HIV Infection
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Probiotics

• Registration Number: NCT01492803
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-11-04
• Study Start: 2011-12
• Study First Submitted QC: 2011-12-14
• Study First Posted: 2011-12-15
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Status Verified: 2016-02
• Last Update Submitted: 2017-02-27
• Last Update Posted: 2017-02-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects randomized to the placebo arm.
Probiotics	Probiotics	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).

Primary Outcome Measures

Name	Time	Method
Plasma LPS levels	32 Weeks	To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS.

Secondary Outcome Measures

Name	Time	Method
Plasma pro-inflammatory cytokines and macrophage activation	32 Weeks	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.
Stool colonization with Lactobacillus plantarum	32 Weeks	To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics.
Lymphocyte activation markers	32 Weeks	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.
Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count	32 Weeks	To examine if probiotics have any impact on quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count among the study cohort.
Stool microbial composition and genetic diversity	32 Weeks	To molecularly characterize changes in overall bacteria diversity within the stool specimens of youth treated with probiotics.
Safety labs and adverse events as a measure of acceptability and tolerability of probiotics	32 Weeks	To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.
Food frequency and probiotics and lifestyle questionnaires	32 Weeks	To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.