Clinical trial NCT01492803: 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
Overall status: WITHDRAWN
Phase: NA
Conditions: HIV Infection
Keywords: HIV infection
Probiotics
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2011-12-15
Enrollment: 0
Sex: ALL
Minimum age (years): 13
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Plasma LPS levels
timeFrame: 32 Weeks
Secondary outcomes:
measure: Stool colonization with Lactobacillus plantarum
timeFrame: 32 Weeks
measure: Plasma pro-inflammatory cytokines and macrophage activation
timeFrame: 32 Weeks
measure: Lymphocyte activation markers
timeFrame: 32 Weeks
measure: Quantitative HIV-1 plasma RNA (viral load) and CD4 T-cell count
timeFrame: 32 Weeks
measure: Stool microbial composition and genetic diversity
timeFrame: 32 Weeks
measure: Safety labs and adverse events as a measure of acceptability and tolerability of probiotics
timeFrame: 32 Weeks
measure: Food frequency and probiotics and lifestyle questionnaires
timeFrame: 32 Weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of South Florida
name: John Sleasman, MD
role: STUDY_CHAIR
References: