Gut Microbiota, Bacterial Translocation, Immune Activation and Endothelial Dysfunction in HIV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Changes in inflammatory markers
研究概览
简要总结
A rapid and almost complete loss of CD4+ T cells from the gut associated lymphoid tissue (GALT) occurs early in HIV infection, with a permanent damage in the intestinal barrier, changes in gut microbiota, increased bacterial translocation and persistent immune activation, changes that are not restored after the initiation of antiretroviral therapy. The investigators hypothesize than an intervention targetting the enterocyte barrier and the gut microbiota might modify the gastrointestinal tract towards a bifidogenic microbiota and improve markers of bacterial translocation, inflammation, immune activation and endothelial dysfunction.
详细描述
This is a randomized placebo-controlled clinical trial to evaluate the safety and effectiveness to modify gut microbiota, bacterial translocation, immune activation and markers of endothelial dysfunction of a dietary supplement (prebiotics + glutamine) during a period of six weeks. The study will enroll four cohorts: 1) HIV-infected, treatment naive individuals; 2) HIV-infected subjects, currently on ART, with >350 CD4+ T-cells/uL; 3) HIV-infected subjects, currently on ART, with <350 CD4+ T-cells/uL; 4) HIV negative healthy controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •After receiving information on the design and objectives of the study, the possible risks involved, and the fact that they can refuse to collaborate at any time, patients will give their informed consent to participate in the study and agree to provide material for the cellular and molecular studies.
- •Aged over 18 years.
- •Group 1: HIV+, Not receiving ART and no previous exposure to ART, at least 2 years since HIV diagnosis.
- •Group 2: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and more than 350 CD4+ T-cells/uL.
- •Group 3: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and less than 350 CD4+ T-cells/uL.
- •Group 4: HIV-, healthy controls.
排除标准
- •Major cardiovascular risk factors.
- •Concomitant acute diseases.
- •Gastrointestinal disorders.
- •Pregnancy.
- •Antibiotic exposure in the previous month.
- •Regular use of foods or supplements containing prebiotics or probiotics within the 2 weeks prior to initiation of the study.
结局指标
主要结局
Changes in inflammatory markers
时间窗: 6 weeks
Changes in interleukine-6 and high-sensitivity C Reactive Protein
Changes in markers of immunoactivation
时间窗: 6 weeks
Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38.
Safety
时间窗: 6 weeks
Adverse events monitoring during the intervention
Changes in markers of endothelial dysfunction
时间窗: 6 weeks
Changes in asymmetric dimethylarginine and flow-mediated dilation
Changes in gut microbiota composition
时间窗: 6 weeks
Changes in gut microbiota as determined by 454 pyrosequencing.
Changes in markers of bacterial translocation
时间窗: 6 weeks
Soluble CD14 and increasing permeability binding protein.
次要结局
- Disease progression in HIV-infected patients.(6 weeks)
- Changes in gut microbiota(6 weeks)
- Thymic function(6 weeks)
- Gene expression in peripheral blood monocytic cells.(6 weeks)
研究者
Sergio Serrano-Villar
Post-Doctoral Researcher
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal