A Phase I/II Randomized, Double-Blind, Placebo Controlled Study of Repeated Low-Dose Fecal Microbiota Restoration in HIV-Infected Subjects. The REFRESH Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to contribute to chronic immune dysfunction. Manipulation of the intestinal microbiota with nutritional interventions exert limited immunologic effects, but a deep understanding of how these interventions could ameliorate gut dysbiosis and influence health among HIV-infected individuals remain unexplored. In this Phase I clinical trial, 30 HIV-infected subjects on effective ART with evidence of persistent immune dysfunction, indicated by a CD4/CD8 ratio<1 will be included and randomized to either repeated low-dose oral fecal microbiota transplantation or placebo during 8 weeks. The primary outcome will be safety. Secondary outcomes will include changes in CD4+ T cell counts, CD8+ T cell counts, CD4/CD8 ratio, inflammatory markers, T cell activation and markers of enterocyte barrier function through week 48. Engraftment on host microbiota will be examined using Illumina sequencing of the V3-V4 16S RNA, and changes in bacterial metabolism and in the plasma metabolite fingerprint will be studied by combination of untargeted mass spectrometry and two different and complementary separation techniques in bacterial and plasma 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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •On stable antiretroviral therapy with plasma HIV RNA <20 copies/mL during at least 48 weeks.
- •CD4/CD8 ratio <1
排除标准
- •Pregnancy
- •Gastrointestinal diseases, including cirrhosis
- •Active infections, including HCV
- •EBV and/or CMV negative patients (donors are not screened for EBV/CMV).
- •Planned used of chemotherapy or antibiotics
- •Allergy to sodium chloride or glycerol (the former components are capsule ingredients Generally Recognized As Safe (GRAS)
- •Current or planned use of antimicrobial agents (including prophylactic treatments against P. jiroveci) other than ART.
- •Neutropenia <500 cells/uL or CD4 counts <350 cells/uL
- •Patients unable to give informed consent
- •Patients unable to comply with the protocol requirements
- •Predicted death within time period of follow-up
- •Any other condition for which the treating physician thinks the treatment may pose a health risk
- •Dysphagia: oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple sclerosis, ALS)
- •History of aspiration
- •History of gastroparesis
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: From baseline through week 48
次要结局
- Changes in CD4/CD8 ratio(From baseline through week 48)
- Changes in microbiota alpha diversity metrics(From baseline through week 48)
- Changes in plasma Interleukin-6 levels(From baseline through week 48)
- Changes in CD4+ T cell counts(From baseline through week 48)
- Changes in CD8+ T cell counts(From baseline through week 48)
- Changes in microbiota Unifrac distances(From baseline through week 48)
- Changes in plasma hs-CRP levels(From baseline through week 48)
- Changes in plasma kynurenine/tryptophan ratio(From baseline through week 48)
- Changes in microbiota Canberra distances(From baseline through week 48)
- Changes in plasma lipoteichoic acid levels(From baseline through week 48)
- Changes in plasma LBP levels(From baseline through week 48)
- Percentage of HLA-DR+/CD38+ T cells in blood(From baseline through week 48)
研究者
Sergio Serrano-Villar
MD, PhD
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal