The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Safety
研究概览
简要总结
HIV progression is closely associated with chronic immune activation driven by leakage of bacterial products from a damaged gut, the investigators largest immunological organ. Notably, the degree of immune activation has been suggested to be a better predictor of disease progression than plasma viral load, and markers of immune activation and gut damage have been identified as therapeutic targets per se. The major damage by HIV to the immune system is an initial massacre of gut mucosal CD4+ Th17 cells. Interestingly, a normal gut flora has been shown to induce the maturation of Th17 cells in the small intestine mucosa. Preliminary reports have shown that the gut flora is altered in HIV-1 infection compared to controls. In this project, the investigators will characterize microbial composition of gut flora in chronic HIV infection with ultradeep sequencing. Gut flora composition will be related to clinical data as well as quantitative data of circulating microbial products and activation markers. Second, in a randomized clinical trial (RCT) the effect of probiotic lactobacilli on HIV pathogenesis and progression will be tested. This Gram-positive strain is clinically tested and is able to colonize the gut.
详细描述
Objectives:
To explore (i) the safety and tolerability, and (ii) the efficacy of probiotics on HIV-associated microbial translocation, systemic immune activation, disease progression and composition of gut microbiota in chronic HIV-1 infection.
Methodology/Study design:
Approximately 50 patients without current indication for antiretroviral treatment (ART) and 50 patients receiving ART without normalised CD4 counts will be included. A controlled clinical trial will be carried out within each stratum randomised in a 2:1:1 fashion to double blinded intervention and placebo arms as well as an open, untreated control arm, respectively.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For patients without ART: Confirmed diagnosis of HIV infection > 6 months and CD4+ T cell count < 900
- •For patients on stable, effective ART: HIV RNA < 50 copies/ml > 6 months and CD4+ T cell count > 500
- •Signed informed consent.
排除标准
- •Severe illness requiring hospitalization
- •Systemic antibiotics or probiotics the last two months
- •Current immune modulating therapy
- •Infectious diarrhea
- •Inflammatory bowel disease
- •Acute primary HIV infection
- •Patients immigrating from Africa, Asia or Latin-America within the last 6 months.
研究组 & 干预措施
Control
No intervention
Probiotics
A multi-strain Probiotic consisting of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk (Biola®, TINE SA, Oslo), 250 mL/day for 8 weeks.
干预措施: Multi-strain probiotic (Dietary Supplement)
Placebo
Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Safety
时间窗: 2 months
Adverse events monitoring during the study period of 2 months
Changes in measures of microbial translocation
时间窗: 2 months
Changes in plasma leves of lipopolysaccharide (LPS) and soluble CD14 from baseline to 2 months (end of study)
Changes in markers of immune activation
时间窗: 2 months
Changes in CD38, HLA-DR and PD-1 on CD8+ and CD4+ T cells from baseline to 2 months (end of study)
次要结局
- Disease progression in untreated patients(2 months)
- Immune reconstitution in ART treated patients(2 months)
- Gut microbiota composition(2 months)
研究者
MariusTrøseid
Marius Trøseid, MD, PhD
Oslo University Hospital