Impact of Propionic Acid on Regulatory T Cell Function in Children With Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in count of regulatory T-cells from baseline to week 4
研究概览
简要总结
Pro-Kids is a multi-center, double-blind, randomized and placebo-controlled intervention study in children with chronic kidney disease. The investigators address the effect of a dietary food supplementation of propionic acid on the immune system and the function of the intestinal barrier in CKD patients treated with hemodialysis.
详细描述
Chronic inflammation is a major risk factor of cardiovascular disease progression in CKD, irrespective of confounding comorbidities. Based on current knowledge, microbially-derived metabolites such as short chain fatty acids (SCFA) play an important role in the regulation of chronic inflammatory processes in CKD patients. Children with CKD are known to have reduced serum levels of the SCFA propionic acid (PA), as a consequence of both gut microbial dysbiosis and reduced fiber intake. In animal and human studies the impact of PA on function and abundance of regulatory T cells (Treg) has been demonstrated. Consequently, the investigators aim to normalize the PA serum levels by oral PA food supplementation in hemodialysis patients in order to mitigate chronic inflammation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight: > 30kg
- •CKD G5 treated with hemodialysis
- •Continuous hemodialysis treatment for > 3 months
- •Clinical stable condition
- •Manifestation of CKD within childhood (<18 years)
排除标准
- •Disease or dysfunctions, which disqualifies the patient
- •Incapacity of contract or any other circumstances, which prohibit the patient or his legal guardians from understanding setup, meaning and entity of the study
- •Acute infections
- •Immunosuppressive therapy within the last 12 weeks before the start of the study
- •Pre-/pro- or postbiotic or antibiotic therapy within the last 4 weeks before the start of the study
- •Planned or unplanned hospitalization within in last 4 weeks before the start of the study or during study
- •Malignant diseases
- •Pregnancy
- •chronic gastrointestinal or hepatic diseases (for example chronic inflammatory bowel disease
- •alcohol- or drug abuse
- •parallel participation on other interventional trials
研究组 & 干预措施
Placebo Intervention
The control-group receives a placebo instead of propionate. The placebo contains maltodextrin and the same amount of sodium chloride as compared to the PA intervention. The placebo is taken twice per day for 28 days.
干预措施: Placebo (Other)
PA Intervention
The group which receives the PA as a dietary food supplement. A single capsule contains 500mg of sodiumpropionate, which is taken twice daily for 28 days.
干预措施: Sodium propionate (Dietary Supplement)
结局指标
主要结局
Change in count of regulatory T-cells from baseline to week 4
时间窗: Baseline visit (week 0) in comparison to week 4
Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood mononuclear cells (PBMC; relative quantification) by flow cytometry.
次要结局
- Cardiovascular Phenotyping(Baseline visit (week 0); Week 2; Week 4; Week 12)
- Cholesterol levels(Baseline visit (week 0); Week 2; Week 4; Week 12)
- Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)(Baseline visit (week 0); Week 2; Week 4; Week 12)
- Single cell RNA sequencing of immune cells(Baseline visit (week 0); Week 4)
- Taxonomy of the fecal microbiome(Baseline visit (week 0); Week 4)
- T regulatory cell (Treg) suppression assay(Baseline visit (week 0); Week 4)
- Propionic acid serum levels and targeted metabolomics(Baseline visit (week 0); Week 2; Week 4; Week 12)
- Intestinal barrier function(Baseline visit (week 0); Week 2; Week 4; Week 12)
研究者
Johannes Benjamin Holle
Principal Investigator
Charite University, Berlin, Germany