Probiotic Visbiome for Inflammation and Translocation in HIV I (PROOV IT I)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Blood immune activation
研究概览
简要总结
Modern antiretroviral therapy (ART) has transformed the clinical care and lived experience of HIV infection. However, increased rates of adverse health conditions that are related to immune activation, such as cardiovascular disease (CVD) and neurodegenerative disease in ART-treated individuals persist. An important cause of this inflammation is the gut CD4 T cell loss and the "leaking" or translocation of luminal gut bacteria and other microbes across the bowel wall and into the bloodstream.
The use of complementary and alternative therapies is common among people living with HIV, however their efficacy has generally not been well demonstrated. Probiotics are live microbes that may provide a health benefit to the host and the investigators believe that the simultaneous use of probiotics along with antiretroviral therapy (ART) will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation.
Probiotic Visbiome consists of a high potency blend of eight different probiotics. The precise mechanism of action of Visbiome is unknown, but preclinical studies have shown that Visbiome may modulate the immune response towards a phenotype that is associated with reduce inflammation, and Visbiome was also protective in a non-human primate model of SIV infection. Therefore, we believe that the "beneficial" bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected individuals as they start ART. Early resolution of gut immune cells may normalize microbial translocation and immune activation and will reduce the rates of HIV-associated comorbidities.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Documented HIV-1 infection
- •Male adult (age >18 years)
- •Antiretroviral therapy-naïve
- •Ability to provide informed consent
- •HIV-1 viral load ≥1,000 copies/ml
排除标准
- •Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
- •Taking pharmaceutical grade probiotics
- •Any of the following abnormal laboratory results in screening:
- •Hemoglobin <85 g/L
- •Neutrophil count <750 cells/μl
- •Platelet count <50,000 cells/μl
- •AST or ALT >5X the upper limit of normal
- •Malignancy
- •Liver fibrosis (decompensated cirrhosis), portal hypertension or clinical hepatitis
- •Other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
研究组 & 干预措施
Probiotic Group
Visbiome experimental group (900 billion bacteria daily; 2 sachets daily)
干预措施: Visbiome (Drug)
Placebo Group
Placebo comparator group
干预措施: Placebo (Other)
结局指标
主要结局
Blood immune activation
时间窗: 24 weeks
Percent of blood immune activation (coexpression of CD38 and HLA-DR) on CD8 T cells at week 24 in participants randomized to probiotic Visbiome versus the placebo arm
次要结局
- Gut HIV DNA levels(24 weeks)
- Number and function of gut immune cells (including CD4 T cell subsets)(24 weeks)
- Tolerability of Visbiome assessed by AE monitoring and participant questionnaire(24 weeks)
- Level of microbial translocation (including LPS and sCD14)(24 weeks)
- Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP)(24 weeks)
- Intestinal permeability (Lac/Mac ratio)(24 weeks)
- Microbiome analysis by 16s rRNA bacterial DNA isolated from gut tissue and anal swabs(24 weeks)
- Canadian Diet History Questionnaire(24 weeks)
- Safety assessed by AE monitoring and participant questionnaire(24 weeks)
- Adherence to probiotic Visbiome assessed by participant questionnaire and sachet count(24 weeks)