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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Dietary Supplement: Probiotics; Dietary Supplement: Placebo	Not Applicable

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Supportive Care
Official Title:	A Randomized Placebo-Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents
Study Start Date :	December 2011
Estimated Primary Completion Date :	December 2012
Estimated Study Completion Date :	December 2012

Arms and Interventions

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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 Name: No other names.

Outcome Measures

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Primary Outcome Measures :

1. Plasma LPS levels [ Time Frame: 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 :

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

Eligibility Criteria

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Ages Eligible for Study:	13 Years to 24 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Sponsors and Collaborators

University of North Carolina, Chapel Hill

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Investigators

Study Chair:	John Sleasman, MD	University of South Florida

More Information

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Additional Information:

ATN website 

Responsible Party:	University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT01492803 History of Changes
Other Study ID Numbers:	ATN 097
First Posted:	December 15, 2011
Last Update Posted:	February 28, 2017
Last Verified:	February 2016

Keywords provided by University of North Carolina, Chapel Hill:

HIV infection; Probiotics

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases	Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases