Effect of 4 Weeks of Oral Probiotic Desulfovibrio Piger Supplementation on Immunological and Metabolic Parameters in Individuals With Longstanding Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Parameters of systemic and intestinal inflammation
研究概览
简要总结
The goal is to establish the effect of oral probiotic Desulfovibrio piger (D. piger) supplementation on immunological and metabolic parameters in individuals with longstanding type 1 diabetes with residual beta cell function. The investigators will perform a double-blind, randomized, placebo-controlled trial in 2x10 participants to measure effects of D. piger on parameters of systemic and intestinal inflammation and residual beta cell function.
详细描述
The investigators perform a double-blind, randomized, placebo-controlled trial with two arms (10 participants per arm, total of 20 participants) in adults with longstanding type 1 diabetes with residual beta cell function. The study duration is 6 weeks, with 4 weeks of intervention in which participants will be given D. piger or placebo once daily and 2 weeks of washout period. The main study enpoints include the changes (versus baseline) in parameters of systemic/intestinal inflammation and beta cell function between the placebo and D.piger-treatment arms at the end of treatment (4 weeks). In addition, any long-lasting effects will be determined by assessing the changes in the above described markers after a 2 week washout period (6 weeks).
Secondary endpoints include glucose variability (continuous glucose monitoring, CGM), fecal microbiome composition (including strain engraftment of D. piger, plasma metabolites), immune cell phenotype and frequency and validated questionnaires (gastro-intestinal complaints) at these three timepoints (0,4,6 weeks).
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
The unblinded researcher will provide the study intervention to the blinded investigator in a coded fashion. Both the investigator and the participant are blinded. In case of emergency, an unblinding protocol is activated.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, age >18 years
- •A diagnosis of type 1 diabetes, with duration of more than 5 years, with minimally one of antiGAD65, IA2, ZnT8 autoantibodies present assessed at diagnosis or routine visits at Diabeter Centrum.
- •Evidence of remaining residual beta cell function with detectable UCPCR (more than 0.01 nmol/mmol C-peptide/creatinine ratio) and or fasting plasma C-peptide more than 0.2 mmol/L.
- •BMI 18-30 kg/m2
排除标准
- •Use of antibiotics or proton-pump inhibitors within the last three months before screening or during study period
- •Use of other probiotic supplementation within the last month before screening or during study period
- •A history of cholecystectomy
- •Overt untreated gastrointestinal disease, inflammatory bowel disease or abnormal bowel habits
- •Absence of a large bowel (ie colostomy)
- •Evidence for comprised immunity (HIV infection, chemotherapy, other autoimmune diseases, systemic anti-inflammatory therapy)
- •History of cardiovascular disaeses (CVD) events
- •Hepatic enzymes>2.5 higher than the upper limit of normal range, determined during MARVEL visits/routine visits
- •Kidney failure (eGFR <15ml.min/1.73m2), dialysis, kidney transplantation,
- •Inability or unwillingness to donate feces or urine.
- •Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
- •Alcohol abuse (equal or above 21 units per week)
- •Inability or unwillingness to provide informed consent.
研究组 & 干预措施
Probiotic Desulfovibrio piger
Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
干预措施: Probiotic dietary supplement (Dietary Supplement)
Placebo
placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Parameters of systemic and intestinal inflammation
时间窗: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
systemic inflammation determined by measuring plasma CRP, and proinflammatory cytokines (IFNgamma, IFN alpha, TNFalpha) intestinal inflammation assessed by LB, iFABP, zonulin in plasma
Residual beta cell function
时间窗: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
Assessed by C peptide AUC during mixed meal tolerance test and/or post meal urine C-peptide/creatinine ratio levels.
次要结局
- Glucose variability(From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.)
- Immune cell phenotypes and frequency(From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.)
- Fecal microbiome composition and strain engraftment(From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.)
- Gastrointestinal Symptom Rating Scale (GSRS)(From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.)
研究者
Max Nieuwdorp
Principal Investigator (prof dr)
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)