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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01492803
First received: November 4, 2011
Last updated: October 8, 2013
Last verified: August 2013

November 4, 2011
October 8, 2013
December 2011
December 2012   (final data collection date for primary outcome measure)
Plasma LPS levels [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS.
Same as current
Complete list of historical versions of study NCT01492803 on ClinicalTrials.gov Archive Site
  • Stool colonization with Lactobacillus plantarum [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics.
  • Plasma pro-inflammatory cytokines and macrophage activation [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    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.
  • Lymphocyte activation markers [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 32 Weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 32 Weeks ] [ Designated as safety issue: Yes ]
    To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.
  • Food frequency and probiotics and lifestyle questionnaires [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
HIV Infection
  • 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.
  • Dietary Supplement: Placebo
    The placebo sticks will contain approximately 1 g maltodextrin
  • Placebo Comparator: Placebo
    Subjects randomized to the placebo arm.
    Intervention: Dietary Supplement: Placebo
  • 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).
    Intervention: Dietary Supplement: Probiotics
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
13 Years to 24 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01492803
ATN 097
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute on Drug Abuse (NIDA)
  • National Institute of Mental Health (NIMH)
Study Chair: John Sleasman, MD University of South Florida
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP