BetaFIT study: Beta cell imaging after Faecal mIcrobiota Transplantation

As the increased T1D incidence is primarily observed in subjects who are not
genetically predisposed, environmental factors have been suggested to play a
role, and these factors have invariably been linked to changes in the gut
microbiome. Indeed, an altered composition of the faecal microbiota composition
was observed in adolescent T1D patients. Faecal Microbiota Transplantation
stops the decline in endogenous insulin production in newly diagnosed type 1
diabetes patients. It is unknown whether this is due to an increase in beta
cell mass, or increased function of the remaining beta cells.
Ga-68-NODAGA-exendin PET/CT imaging offers a unique opportunity to further
elucidate the effects of Faecal Microbiota Transplantation on beta cells. With
this tracer, we can quantify beta cell mass in people received faecal
microbiota transplantation. Using this quantification, we will correlate the
beta cell mass to the beta cell function. Beta cell function is derived in the
following previous studies: ENCAPSULATE-DM1 or FMT preserve-DM1. This will help
us to understand how to prolong or even consolidate the *honeymoon phase* in
T1D, which will decrease patient dependence on insulin injections or infusions.
The first period with relative preserved beta cell function is also called the
*honeymoon period*. Extension of this period greatly assists in the ease of
blood glucose levels in these patients during a longer period of time, and thus
supposedly increases quality of life.

The primairy objective of this study is to investigate whether beta cell mass
is correlated to beta cell function after autologous faecal microbial
transplantation (FMT) in patients with newly diagnosed type 1 diabetes after
FMT. Within 1 month after completed participation in the ENCAPSULATE-T1D or FMT
preserve-T1D trial, beta cell mass is visualised and quantified by using
68Ga-NODAGA-exendin PET/CT imaging. Beta cell function is derived in the
following previous studies: ENCAPSULATE-DM1 or FMT preserve-DM1.

Patients will be recruited from the participants who have completed the
ENCAPSULATE-DM1 or FMT preserve-DM1 study. The subjects must have a minimum age
of 18 years. After recruitment, subjects will visit the Department of Radiology
and Nuclear Medicine in the Radboudumc in Nijmegen. Participants will be asked
to fast 4 hours and to terminate shortacting insuline 6 hours prior to the
visit. After signing informed consent, metabolic characterization is performed
that will consist of laboratory parameters (fasting glucose, HbA1c, c-peptide,
creatinine, ALAT, ASAT).
68Ga-NODAGA-exendin PET/CT scans will be performed. All patients will be
injected with 100 ±10% MBq 68Ga-NODAGA-exendin, followed by monitoring the
blood pressure and blood glucose. One hour after injection, a static PET/CT
scan will be made followed by a low-dose CT scan without contrast agent will be
made for anatomical correction. Quantitative analysis of the scans will be
performed for determination of binding capacity and absolute uptake in the
pancreas. Analysis of patient data (imaging, metabolic testing) will be
performed and descriptive statistics will be obtained.

The participants will have to complete a visit at the department of Nuclear
Medicine in Radboudumc. During this visit, a short physical exam concerning
biometric parameters (weight, height) will be performed. They will undergo a
68Ga-NODAGA-exendin PET/CT scan once. After intravenous administration of the
radiopaharmaceutical, blood glucose levels and blood pressure will be
monitored. Single cases of low blood pressure and low blood glucose levels have
been observed at higher doses of Byetta® (exenatide). In addition, high doses
of Byetta® may result in nausea and headaches. In this study, no (serious)
adverse events will be expected since we will inject 100 ±10% MBq
68Ga-NODAGA-exendin corresponding to a dose of 4 to 7 ug. The radiation
exposure is considered minimal to little, because it will not exceed 5.5 mSv.
Due to the placement of intravenous catheter, there is a small chance of
bruising, pain and inflammation at the site of catheter placement.

Despite the radiation exposure, 68Ga-exendin PET can be used to provide in vivo
visualization and quantification of tissues expressing the GLP-1 receptor. This
study will contribute to an improved understanding of the role of faecal
microbiota transplantation on beta cell mass preservation in type 1 diabetes.
This will help us to understand how to prolong or even consolidate the
*honeymoon phase* (the first period with relative preserved beta cell functon)
in T1D, which will decrease patient dependence on insulin injections or
infusions. Extension of this period greatly assists in the ease of blood
glucose levels in these patients during a longer period of time, and thus
supposedly increases quality of life.