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

HIV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01492803
• Other study ID #: ATN 097
• Status: Withdrawn
• Phase: N/A
• First received: November 4, 2011
• Last updated: February 27, 2017
• Start date: December 2011
• Est. completion date: December 2012

Study information

• Verified date: February 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 24 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

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)
• Placebo
The placebo sticks will contain approximately 1 g maltodextrin

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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 (TNFa), interferon alpha (IFNa), interleukin-1 beta (IL-1ß), 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   ATN website