Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Renal function
研究概览
简要总结
E. coli Nissle (EcN) is a well-established human probiotic. However, it has been found that it produces colibactin, linked to colorectal cancer. In this safety trial, the safety and properties of a novel, colibactin-knockout EcN strain (EcNΔClbP) is investigated.
详细描述
In this randomised controlled intervention study, the investigators will compare EcN vs. EcN colibactin-knockout (EcNΔClbP), given once daily for 7 days, in a population of healthy individuals. Safety will be established using adverse event reporting, study visits and laboratory parameters. Pharmacokinetics will be established at the beginning and the end of the study. EcN/EcNΔClbP gut engraftment properties and effects on gut microbiome composition will be assessed using fecal analyses (qPCR, shotgun metagonmics). In addition, effects on glucose homeostasis will be studied using continuous glucose monitoring.
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)
盲法说明
Participants will be randomised through Castor (eCRF). Treatment allocation is blinded for investigators and participants. The pharmacist has access to the randomisation list.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female of Caucasian descent
- •If female, postmenopausal
- •Age: 18-65 years old
- •BMI: 18-25 kg/m2
- •Subjects should be able to give informed consent
排除标准
- •Use of any systemic medication (except for paracetamol), including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period.
- •Use of the EcN probiotic strain (Mutaflor®) in the past 12 months.
- •(Expected) prolonged comprised immunity (e.g. due to recent cytotoxic chemotherapy or human immunodeficiency viruses (HIV) infection with a CD4-T cell count < 240/mm3).
- •History of moderate to severe disease of the digestive tract, such as celiac disease, chronic diarrhoea (≥3 stools/day for >4 weeks), chronic obstipation (<2 defecations/week for >3 months), Irritable Bowel Syndrome (IBS) (according to Rome IV criteria) or Inflammatory Bowel Disease (IBD).
- •Any gastro-intestinal disorder within the past 6 months
- •Smoking or illicit drug use (e.g. amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
- •Use of >21 units of alcohol per week on average in the past three months or use of >2 units of alcohol during the study period.
- •Simultaneous participation in other studies
结局指标
主要结局
Renal function
时间窗: Weekly, during 3 weeks
Changes in renal function, expressed as kreatinin levels (micromol/L) throughout the study
Hemoglobin
时间窗: Weekly, during 3 weeks
Changes in hemoglobin in mmol/L throughout the study
basophils
时间窗: Weekly, during 3 weeks
Changes in basophils in 10\^9/L throughout the study
monocytes
时间窗: Weekly, during 3 weeks
Changes in monocytes in 10\^9/L throughout the study
Leucocytes
时间窗: Weekly, during 3 weeks
Changes in leucocytes (10\^9/L)
Bilirubin
时间窗: Weekly, during 3 weeks
Changes in bilirubin in micromol/L throughout the study
gamma-GT in U/L
时间窗: Weekly, during 3 weeks
Changes in gamma-GT in U/L throughout the study
Adverse events
时间窗: 3 weeks
The number, duration and severity of adverse reactions to assess the safety/tolerability of the EcNΔClbP strain compared to the wild type strain.
ALT
时间窗: Weekly, during 3 weeks
Changes in ALT in U/L throughout the study
eosinophils
时间窗: Weekly, during 3 weeks
Changes in eosinophils in 10\^9/L throughout the study
Homeostatic model of insulin resistance (HOMA-IR)
时间窗: Weekly, during 3 weeks
Changes in HOMA-IR throughout the study
Bristol Stool Chart
时间窗: Weekly, during 3 weeks
Changes in Bristol Stool Chart score throughout the study. Stools can be scored from 1 (hard stool) to 7 (watery stool). A score of 4 is considered ideal.
CRP
时间窗: Weekly, during 3 weeks
Changes in CRP (mg/L)
AST
时间窗: Weekly, during 3 weeks
Changes in AST in U/L throughout the study
neutrophils
时间窗: Weekly, during 3 weeks
Changes in neutrophils in 10\^9/L throughout the study
Lipid profile
时间窗: Weekly, during 3 weeks
Changes in lipid profile throughout the study
Gastro-intestinal quality of life - questionnaire
时间窗: Weekly, during 3 weeks
Changes in Gastro-intestinal quality of life (GIQLI) score. The maximum score is 155, the minimum score is 31. A higher score represents a better outcome.
alkaline phosphatase
时间窗: Weekly, during 3 weeks
Changes in alkaline phosphatase in U/L throughout the study
trombocytes
时间窗: Weekly, during 3 weeks
Changes in trombocytes in 10\^9/L throughout the study
次要结局
- Number of copies of EcN (qPCR)(Daily during 2 weeks)
- Microbiome composition(Weekly during 3 weeks)
研究者
Max Nieuwdorp
Prof. dr.
Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)