Encapsulated Faecal Microbiota Transplantation to Preserve Residual Beta Cell Function in Patients With Recently-Diagnosed Type 1 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Preservation of residual beta cell insulin secretion capacity
研究概览
简要总结
In this single arm pilot study it will be investigated whether encapsulated autologous fecal microbiota transplantation may be used to halt the decline in residual beta cell function in individuals with recent onset Type 1 diabetes mellitus.
详细描述
Rationale: The (small) intestinal microbiota composition has been implicated to play an important role in (human) metabolism, as well as autoimmune diseases such as type 1 diabetes mellitus. Faecal microbiota transplantation (FMT) has been shown to significantly alter the microbiota composition, without any serious side effects. It was recently demonstrated that multiple infusions of own faeces (autologous) preserved residual beta cell function up to one year after start of the FMT. Encapsulated autologous FMT provides a safe and feasible option for prolonged treatment on a daily basis, which might stabilize the beta-cell destruction and extend or even bring back the honeymoon period (wherein individuals with recently diagnosed T1D remain wellregulated with minimal doses of insulin).
Objective: confirm the efficacy and feasibility of daily ingested encapsulated freeze-dried autologous (own) faecal matter on the preservation of residual beta cell function as assessed by C-peptide release upon a mixed meal test (MMT) in recently diagnosed type 1 diabetes mellitus (T1D).
Study design: Open label study Study population: Recently diagnosed (0.5-3.5 years of diagnosis) patients with T1D (n=10, aged 18-65 years, BMI 18-30 kg/m2, male/female).
Intervention: After inclusion in the study and a run-in period of 3 months, stools of the participants will be collected and processed into freeze-dried faecal microbiota capsules, which will be ingested daily for 3 months. Participants will be followed for 9 months after inclusion.
Main study parameters/endpoints: The primary endpoint is long-term preservation of beta cell insulin secretion capacity as assessed by stimulated C-peptide AUC0-120min response upon MMT (at -3, 0, 3 and 6 months). The secondary endpoint pertains to changes in plasma biochemistry (HbA1c levels), glucose time-in-range (Freestyle Libre) and subsequent exogenous insulin dose use at -3, 0, 3 and 6 months. The tertiary endpoint is changes in faecal gut microbiota composition at -3, 0, 3 and 6 months, as well as small intestinal microbiota (duodenal biopsy via gastroscopy at 0 and 3 months).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- 否
入选标准
- •In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- •Male or female recently diagnosed (0.5-3.5 years) with type 1 diabetes mellitus.
- •Age: 18-65 years
- •BMI: 18-30 kg/m2
- •Remaining residual beta cell function: detectable plasma C-peptide or urinary Cpeptide at inclusion of the study
排除标准
- •A potential subject who meets any of the following criteria will be excluded from participation in this study:
- •History or symptoms of other autoimmune disease (e.g. hypo- or hyperthyroidism, rheumatoid arthritis).
- •(Expected) prolonged comprised immunity (e.g. due to recent cytotoxic chemotherapy or human immunodeficiency virus (HIV) infection with a CD4 count < 240/mm3).
- •History of a 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).
- •Use of antibiotics, antacid drugs or proton pump inhibitors in the past 3 months or during the study period.
- •Use of pro-/prebiotics in the past three months or during the study period.
- •Smoking or illicit drug use (e.g. MDMA/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.
- •Pregnancy or breast feeding.
- •Inability to provide informed consent.
结局指标
主要结局
Preservation of residual beta cell insulin secretion capacity
时间窗: at -3, 0, 3 and 6 months.
assessed by maximal C-peptide release (residual beta cell function) upon an MMT, AUC0-120 (mmol/ll x min) will be calculated.
次要结局
- HbA1c(At -3, 0, 3 and 6 months.)
- Fecal microbiota composition(At -3, 0, 3 and 6 months.)
- Questionnaire(At -3, 0, 3 and 6 months.)
- Glycaemic control(At -3, 0, 3 and 6 months.)
- Dietary intake(At -3, 0, 3 and 6 months.)
- Small intestinal microbiota composition(Fecal: At -3, 0, 3 and 6 months. Duodenal biopsy: 0 and 3 months)
研究者
Nordin Hanssen
Internist-endocrinologist, Principial investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)