Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents
Primary Purpose
HIV Infection
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Probiotics
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for HIV Infection focused on measuring HIV infection, Probiotics
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Probiotics
Arm Description
Subjects randomized to the placebo arm.
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).
Outcomes
Primary Outcome Measures
Plasma LPS levels
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
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
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
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
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
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
To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.
Food frequency and probiotics and lifestyle questionnaires
To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.
Full Information
NCT ID
NCT01492803
First Posted
November 4, 2011
Last Updated
February 27, 2017
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT01492803
Brief Title
Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents
Official Title
A Randomized Placebo-Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Withdrawn
Study Start Date
December 2011 (undefined)
Primary Completion Date
December 2012 (Anticipated)
Study Completion Date
December 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
Keywords
HIV infection, Probiotics
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to the placebo arm.
Arm Title
Probiotics
Arm Type
Experimental
Arm Description
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 Type
Dietary Supplement
Intervention Name(s)
Probiotics
Other Intervention Name(s)
No other names.
Intervention Description
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)
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
The placebo sticks will contain approximately 1 g maltodextrin
Primary Outcome Measure Information:
Title
Plasma LPS levels
Description
To determine if once daily probiotic therapy decreases microbial translocation in HIV-infected youth as measured by changes in plasma LPS.
Time Frame
32 Weeks
Secondary Outcome Measure Information:
Title
Stool colonization with Lactobacillus plantarum
Description
To quantify the extent that Lactobacillus plantarum populates fecal samples obtained over time in HIV-infected youth receiving probiotics.
Time Frame
32 Weeks
Title
Plasma pro-inflammatory cytokines and macrophage activation
Description
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.
Time Frame
32 Weeks
Title
Lymphocyte activation markers
Description
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.
Time Frame
32 Weeks
Title
Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count
Description
To examine if probiotics have any impact on quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count among the study cohort.
Time Frame
32 Weeks
Title
Stool microbial composition and genetic diversity
Description
To molecularly characterize changes in overall bacteria diversity within the stool specimens of youth treated with probiotics.
Time Frame
32 Weeks
Title
Safety labs and adverse events as a measure of acceptability and tolerability of probiotics
Description
To examine the acceptability and tolerability of probiotics when administered to HIV-infected youth.
Time Frame
32 Weeks
Title
Food frequency and probiotics and lifestyle questionnaires
Description
To explore the effect of diet, smoking, and dietary supplements on plasma pro-inflammatory cytokine levels.
Time Frame
32 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Sleasman, MD
Organizational Affiliation
University of South Florida
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Adolescents
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