Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- BCG vaccine respone
研究概览
简要总结
The primary objectives of this study are to evaluate the effect of early-life B. infantis Rosell®-33 supplementation in infants exposed to HIV on:
- gut microbiome composition and diversity at 4 weeks of life
- markers of intestinal inflammation and microbial translocation at 4 weeks of life
- Th1 cytokine responses to BCG at 7 weeks and 36 weeks of life
The secondary objectives include to evaluate the effect of B. infantis Rosell®-33 supplementation on:
- longitudinal succession of the gut microbiota composition, diversity and function
- relative and absolute abundance of B. infantis in infant stool during the first 36 weeks of life
- stool metabolome
- T cell subset ontogeny during the first 9 months of life.
Exploratory objectives are to evaluate whether B. infantis Rosell®-33 supplementation improves:
- infant growth
- all-cause morbidity
- neurodevelopment during the first 9 months of life
- antibody responses to early childhood vaccines
详细描述
Infants who are born to mothers with HIV (exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, a randomized trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU will be conducted.
This is a parallel, randomised, controlled study. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 x109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 0 Days 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Severe illnesses, e.g. Sepsis
- •current TB or known household TB contact
- •Chronic disorder or medications (other than antiretrovirals and cotrimoxazole prophylaxis) that in the opinion of the investigator would alter immunity
- •Pregnancy or delivery complications including birth asphyxia, seizures, sepsis, major congenital anomalies or congenital infections
- •Known contraindications to components of the interventional products
- •Taking additional probiotics or prebiotics
- •Any condition that in the opinion of the investigator would make participation in the trial unsafe
结局指标
主要结局
BCG vaccine respone
时间窗: 36 weeks of age
Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.
Gut microbiome
时间窗: 4 weeks of age
Alpha (Shannon) and Beta (Bray Curtis and UniFrac) diversity metrics on the entire microbial communities, assessed by bacterial shotgun metagenomics of infant stool, will be compared between treatment arms
Markers of intestinal inflammation and microbial translocation
时间窗: 4 - 36 weeks of age
Concentration of markers of intestinal inflammation and microbial translocation (Lipocalin-2 (Lcn-2), sCD163, I-FABP and LBP measured by ELISA in infant plasma) will be compared cross-sectionally at each time point between groups using Mann-Whitney U tests
次要结局
- Longitudinal succession in gut microbiota composition, diversity and function(4 - 36 weeks of age)
- Stool metabolome(4 weeks of age)
- T cell subsets frequencies(4 - 36 weeks of age)
研究者
Anna-Ursula Happel
Professor
University of Cape Town