Faecal Autologous Capsule Transplantation for Type 1 Diabetes Mellitus

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.

Conditions

• Type 1 Diabetes Mellitis
• Type 1 Diabetes (T1D)
• Fecal Microbiota Therapy (FMT)

Interventions

BIOLOGICAL

freezedried autologous encapsulated fecal microbiota transplantation

The freezedried autologous encapsulated microbiota transplantation increases the exposure of the small intestine to the microbiota residing in the colon. Prior evidence was found that this has strong immunomodulatory effects leading to potential preservation of beta cell function in type 1 diabetes.

OTHER

placebo matching capsule without microbial content

this is the matching placebo capsule that looks from the outside identical to the actual treatment but does not contain the fecal microbiota.

Sponsors & Collaborators

• Diabeter Centrum Amsterdam

  collaborator UNKNOWN

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-30

Primary Completion

2029-09-30

Completion

2029-09-30

Countries

• Netherlands

Study Locations