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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This study has been withdrawn prior to enrollment.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: May 8, 2014
Last verified: May 2014
  Purpose

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 Intervention
HIV Infection
Dietary Supplement: Probiotics
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 0
Study Start Date: December 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   13 Years to 24 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01492803

Sponsors and Collaborators
Investigators
Study Chair: John Sleasman, MD University of South Florida
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01492803     History of Changes
Other Study ID Numbers: ATN 097
Study First Received: November 4, 2011
Last Updated: May 8, 2014
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
HIV infection
Probiotics

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014