A Double Mask Randomized Placebo- Controlled Trial of Probiotics to - PowerPoint PPT Presentation

A Double Mask Randomized Placebo- Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Youth A multi-center clinical trial sponsored by the Adolescent Trials Network (NICHD) Protocol Chairs- John Sleasman and Grace Aldrovandi

Altered GIT fuels immune activation • Mayhem that occurs to mucosal surfaces after acute infection damages immunological and structural GI barrier allowing intestinal microbial products to cross over to the “other side” • Systemic microbes and microbial products stimulate the adaptive and innate immune systems and exacerbate immune activation – Microbial translocation Brenchley et al Nat Immunol 2006

Postulated role for probiotics on MT and induction of immune tolerance in the GI track Science, 307, 1920 (2005)

STUDY POPULATION • HIV-infected youth 13-24 years of age inclusive • Acquired HIV infection > 10 years of age • Absolute CD4 T-cell count > 350 cells/ul • Cohort 1: Not receiving ART with HIV-1 plasma RNA < 50,000 copies/ml • Cohort 2: Currently receiving ART (>24 weeks) prior to entry and quantitative HIV-1 plasma RNA < 400 copies/ml

PRIMARY OBJECTIVE • To determine if once daily probiotics ( L plantarum 299/299v ) decreases microbial translocation in HIV-infected youth based on changes in plasma LPS. • Sample size: 80 subjects (Cohort 1 = 40, Cohort 2 = 40) • Study Duration: 24 weeks on intervention, 32 weeks on study.

Secondary Objectives • Quantify extent that L plantarum with fecal samples over time • Evaluate impact of probiotics on plasma pro- inflammatory cytokines levels and extent of Macrophage and T cell activation • Examine effect of probiotics HIV-1 plasma viral load and CD4 T-cell subsets • Molecularly characterize changes in overall bacteria diversity within the stool specimens fro youth treated with probiotics

Barriers • Identification of effective probiotic likely to colonize the GI tract • Developing CTA/MTA with foreign company • Shifting guidance from FDA regarding the use of probiotics in clinical trials – IND application – GMP standards for “food products” – Are these agents biologicals, therapeutic agents, or food supplements?