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 This is a placebo controlled, double blind, single-centre study. After the randomisation, in a 1:2 (placebo:LFMC) ratio using a validated variable block randomization model in Castor, stratified for sex with block sizes 4,6 and 8, participants will ingest the autologous LFMCs or placebo daily for 6months, which will be followed by a follow-up period of 6months. In total, participants will be followed for12months after inclusion.
Study visits Subjects will in principle visit 3 times in total for this study, with 1 prior screening visit that essentially encompasses participation in the MARVEL cohort (NL85375.018.23, measuring residual beta cell function and questionnaires) and one visit to pick up the second batch of capsules. Each visit will take 180 minutes (maximum of 12 hours over 12 months).
Screening Blood will be drawn for basic biochemistry and patients will hand in the food diaries, questionnaires. In addition, height, weight, blood pressure will be measured and BMI will be calculated. As the faeces is needed to produce the autologous LFMCs, participants are instructed to collect at least 300 grams of fresh faeces. If the fresh faeces is insufficient (\<300g), participants are asked to collect more fresh faeces and bring thisto the AMC at a later date (but before the baseline visit).
Optional: additional fecal collections. It may be the case that individuals produce insufficient feces at once, in that case participants are asked to bring in addition samples until 300g is reached.
Visit1: baseline visit (0 months) At baseline a MMT will be performed, blood will be drawn for basic biochemistry and patients will hand in the food diaries, questionnaires and their fecal and 2h post-meal urine sample. Thereafter, the participant will start with the LFMCs for 6months. The first capsule is ingested with the investigator present to ensure the participant tolerates the capsules well and has an appropriate intake technique.
Visit 2 (3months): by phone to evaluate compliance and potential side-effects.
Visit3: follow-up visit (6months) During this visit the MMT will be repeated, blood will be drawn for basic biochemistry and patients will hand in the food diaries and questionnaires and their 2h post-meal urine sample. In addition, height, weight, blood pressure are measured again. Participants stop with the LFMCs and return any remaining capsules to the investigator.
Visit4: follow-up visit (12months) During this last visit, the MMT will berepeated, blood will be drawn for basic biochemistry and patients will hand in the food diaries, questionnaires and their 2h post-meal urine sample. In addition, height, weight, blood pressure are measured again.
