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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infection
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotics

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 Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects randomized to the placebo arm.	Dietary supplement: Placebo; The placebo sticks will contain approximately 1 g maltodextrin
Experimental: 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).	Dietary supplement: Probiotics; 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); Other Names: No other names.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: John Sleasman, MD, University of South Florida

Publications and helpful links

Helpful Links

• ATN website

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: November 4, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Probiotics; HIV infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ATN 097