Faecal Autologous Capsule Transplantation for Type 1 Diabetes Mellitus
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Preservation of residual beta cell insulin secretion capacity
Study Overview
Brief Summary
SUMMARY
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. In a proof-of-principle study it was found that encapsulated autologous FMT provides a safe and feasible option for prolonged treatment on a daily basis, which might stabilize the beta-cell destruction. These exciting findings are potentially transformative for clinical practice and deserve replication in a larger placebo-controlled trial.
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 amixed meal test (MMT) in recently diagnosed type 1 diabetes mellitus (T1D).
Study design: double-blind placebo-controlled study Study population: n=110, recently diagnosed (<100 days of diagnosis) patients with T1D, aged 18-45 years, BMI 18-30 kg/m2, male/female.
Intervention: After inclusion and randomisation individuals will receive for 6 months either placebo or freeze-dried autologous encapsulated FMT in a 1:2 ratio. Subsequently, participants with be followed for 6 months whether beta cell preservation was durable after cessation of treatment.
Main study parameters/endpoints: The primary endpoint is long-term preservation of beta cell insulin secretion capacity as assessed by stimulated C-peptide AUC0-120minresponse upon MMT (at0, 6 and 12months).The secondary endpoint pertains to changes in post-meal urinary C-peptide levels, plasma biochemistry (HbA1c levels),glucose time-in-range and subsequentexogenous insulin dose use at 0, 6 and 12months.
Nature and extent of the burden and risks associated with participation,benefit and group relatedness: This study is considered a low-risk study, 3MMTs will be performed, for which 70 ml of blood samples will be drawn each visit. As of today, no severe adverse events as result of FMT have been reported in this centre and in the ENCAPSULATE trial investigating the feasibility and safety of this approach participants only reported some minor and transient constipation. In addition, the use of autologous faeces comes with a lower(absent)risk for transmitting any unknown pathogens compared to an allogenic FMT. As there currently is no widely applied therapy to preserve beta cell function in type 1 diabetes, encapsulated autologous FMT can have a potential benefit for the participants.
Detailed Description
OBJECTIVES This study is designed to confirm whether a microbial intervention based on capsules containing autologous (own) lyophilized faecal microbiota, LFMCs, taken daily for 6 months has beneficial effects on residual beta cell function (C-peptide secretion uponMMT) in recently diagnosed type 1 diabetes mellitus compared to placebo. A parallel objective is to assess the impact on glycaemic control.
To investigate the effect of daily oral intake of autologous LFMCs on:
I Preservation of residual beta cell insulin secretion capacity: assessed by maximal C-peptiderelease(residual beta cell function)upon an MMT, AUC0-120min at 0,6 and 12 months. As an additional marker of residual beta cell function, at home post-meal urinary C-peptide levels will be used.
II Glycaemic control: changes in plasma biochemistry (glucose, HbA1c), glucose time in range (FreestyleLibre), urine (microalbuminuria) and subsequent exogenous insulin dose use at 0,6 and 12months.
III Questionnaires and dietary intake: validated questionnaires for abdominal complaints, diabetic complications and hypoglycaemia frequency at 0,6 and 12 months. Dietary intake will be registered via online dietary lists at 0,6 and 12months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female recently diagnosed (<100 days) with type 1 diabetes mellitus.
- •Age:18-45 years
- •BMI: 18-30 kg/m2
- •Remaining residual beta cell function: detectable plasma C-peptide or urinary C-peptide at inclusion of the study.
Exclusion Criteria
- •Major systemic illness
- •(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) or Inflammatory Bowel Disease (IBD).
- •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.
Arms & Interventions
Placebo
Intervention: placebo matching capsule without microbial content (Other)
Encapsulated autologous fecal microbiota transplantation
Intervention: freezedried autologous encapsulated fecal microbiota transplantation (Biological)
Outcomes
Primary Outcomes
Preservation of residual beta cell insulin secretion capacity
Time Frame: At baseline, at 6 months upon completion of treatment and at 12 months after intiation of treatment
measured by plasma C-peptide in mixed meal and 2hour post meal urine sample
Secondary Outcomes
- exogenous insulin dose(At baseline, at 6 months upon completion of treatment and at 12 months after intiation of treatment)
- Hba1c(At baseline, at 6 months upon completion of treatment and at 12 months after intiation of treatment)
- Continuous glucose monitoring(At baseline, at 6 months upon completion of treatment and at 12 months after intiation of treatment)
- albuminuria(At baseline, at 6 months upon completion of treatment and at 12 months after intiation of treatment)
Investigators
Nordin Hanssen
Associate Professor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)