ALLOGENEIC FAECAL MICROBIOTA, POOLED for Type 2 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- For patients : Adult patients from 18-65 years old\n- For donors : Euglycemic: fasting glycemia <6mmol/l; Hba1c <5.9%\n- For donors : Healthy no current drug prescription (except contraception or pain killers other than AINS)\n- For donors : Regular bowel movement in the morning defined as 1 stool/day at least\n- For donors : Signature of the informed consent\n- For donors : Subject with health insurance (except AME)\n- For patients : T2D patients any severity of initial T2D disease before BS\n- For patients : Who underwent Bariatric surgery (BS) 1 to 5 years before (Roux-en-Y gastric bypass or sleeve, patients with pre-BS BMI≥35kg/m²)\n- For patients : Non-Diabetic remission (NDR) patients 1-year post-BS, defined as Hba1c>6.5% and/or fasting glycaemia>6.9mmol/l and/or receiving anti-diabetic drugs for at least 2 months. We will rather select patients with uncontrolled diabetes with Hba1c>7% and willing to receive proton pump inhibitor (PPI)\n- For patients : Patient compliant to 1rd year follow-up post-BS (who came to at least 2 among the three routine care follow-up visits during the first year (i.e. 3, 6 and 12M)\n- For patients : Signature of the informed consent\n- For patients : Affiliated to a social security regime (except AME)\n- For donors : Age ≥ 18 years and < 50 years\n- For donors : Lean individuals (18"}

Exclusion criteria

• {"criterion_text":"- For patients : Type 1 diabetes\n- For patients : Patient under guardianship or curatorship\n- For donors : Familial history of obesity or diabetes and personal history of overweight/obesity\n- For donors : Infectious risk (for more information see the protocol)\n- For donors : Gastrointestinal disease (for more information see the protocol)\n- For donors : Personal or 1st degree family history of autoimmune or inflammatory disease (inflammatory arthritis, psoriasis, multiple sclerosis, type I diabetes, Hashimoto…)\n- For donors : Factors that may affect the composition of the intestinal microbiota (Special Diet - exclusion diet, vegetarian diet) /Taking immunosuppressants - eg calcineurin inhibitors, corticosteroids, biological agents, etc. / Chemotherapy / Subject with a chronic illness / Curative long-term treatment\n- For donors : Exclusion criteria according screening test : 1/Positive result for one of the contagious diseases testing blood and stool, excepting for IGG positive EBV, CMV and toxoplasma serology according to ANSM recommendations and only positive Ac HBS HBV witness of post-vaccination immunity and HAV Healed / 2 -\tCarrier of multiresistant bacteria / 3- -\tAbnormal biological test at inclusion suggesting a pathology: fasting blood glucose, Hba1c, blood count, chemistry panel with determination of urea and creatinine, liver function tests (AST, ALT, GGT, PAL, bilirubin), CRP, hemostasis\n- For donors : Pregnancy or breastfeeding women\n- For donors : Subject under guardianship or curatorship\n- For donors : Subject deprived of their liberty by a judicial or administrative decision\n- For patients : Patient deprived of their liberty by a judicial or administrative decision\n- For donors : Temporary donor’s exclusion criteria - Infectious risk (for mors information see protocol)\n- For patients : Patients receiving antibiotics (ATB) at the selection time or within the 3 previous months (if agreeing to participate to the study, the patients will be proposed randomization 3 months after stopping ATB)\n- For patients : Immunosuppressive therapy\n- For patients : Laxative treatments\n- For patients : DR since BS (nor relapse patients detailed further in the protocol)\n- For patients : Patients already recruited in another interventional studies study where a drug is being tested\n- For patients : Pregnant or breastfeeding women\n- For patients : Patient with contemporary disease such as intestine disease"}

Primary endpoints

• {"endpoint_text":"- Hba1c change from baseline to 6 months post randomization (we expect at least -0.75%)","definition_or_measurement_approach":"Change in HbA1c from baseline to 6 months (24 weeks) post-randomization; HbA1c measured and compared baseline vs 6 months (primary effect size expected approximately -0.75%)."}

Secondary endpoints

• {"endpoint_text":"- Evolution of Hba1c from baseline to 2 years post randomization Hba1c will be measured at the following visits: baseline 6, 12, 18, 24W, 1 and 2 years post randomization","definition_or_measurement_approach":"HbA1c measured at baseline, 6, 12, 18, 24 weeks, 1 year and 2 years; change from baseline to 2 years."}
• {"endpoint_text":"- Evolution of C-peptide from baseline to 2 years post randomization C-peptide will be measured at the following visits: baseline 6, 12, 18, 24W, 1 and 2 years post randomization","definition_or_measurement_approach":"C-peptide measured at baseline, 6, 12, 18, 24 weeks, 1 year and 2 years; change from baseline to 2 years."}
• {"endpoint_text":"- Evolution of insulin secretion from baseline to 24W using the HOMA-B calculator (=20 × fasting insulin (μIU/ml)/ fasting glucose (mmol/ml) − 3.5)","definition_or_measurement_approach":"Insulin secretion evaluated from baseline to 24 weeks using HOMA-B formula (=20 × fasting insulin (μIU/ml) / fasting glucose (mmol/ml) − 3.5)."}
• {"endpoint_text":"- Evolution of insulin resistance from baseline to 24W: we will use the HOMA-IR (= fasting insulin (μIU/ml) × fasting glucose (mmol/ml)/ 22.5) and Disse index (=Disse 12*((2.5*(HDL-total cholesterol)-NEFA)-insulin)) which are two complementary markers to evaluate insulin resistance using different parameters.","definition_or_measurement_approach":"Insulin resistance assessed from baseline to 24 weeks using HOMA-IR (fasting insulin × fasting glucose /22.5) and Disse index (formula provided)."}
• {"endpoint_text":"- Glycaemia profile (using glycemic holter) changes from baseline to 6W and 24W","definition_or_measurement_approach":"Continuous glycaemic monitoring (glycemic holter) with changes evaluated from baseline to 6 and 24 weeks."}
• {"endpoint_text":"- Number of antiT2D drugs. The number of concomitant anti-diabetic drugs will be analysed at baseline and at 1 and 2 years’ post-randomization.","definition_or_measurement_approach":"Count of concomitant anti-diabetic medications at baseline, 1 year and 2 years; comparison over time."}
• {"endpoint_text":"- Type of antiT2D drugs. The type of anti-diabetic drugs will be analysed at baseline and 1 and 2 years’ post-randomization, modifications will be described.","definition_or_measurement_approach":"Type/class of anti-diabetic drugs recorded at baseline, 1 year and 2 years; descriptive analysis of modifications."}
• {"endpoint_text":"- Number of patients reaching DR. Proportion of patients reaching DR (partial or complete) at 24W and maintaining it at 1 and 2 years. Partial diabetes remission (PDR) is defined as Hba1c <6.5% and FPG <7.0 mmol/l without the need of glucose- lowering agents. Complete diabetes remission (CDR) is defined as Hba1c <6.0% and FPG <5.6 mmol/l without glucose-lowering agents","definition_or_measurement_approach":"Proportion achieving partial or complete diabetes remission at 24 weeks and maintaining at 1 and 2 years. Definitions: PDR Hba1c <6.5% and FPG <7.0 mmol/l without glucose-lowering agents; CDR Hba1c <6.0% and FPG <5.6 mmol/l without agents."}
• {"endpoint_text":"- Proportion of patient needing a “safety” glucose lowering treatment to control Hba1c despite FMTs","definition_or_measurement_approach":"Proportion requiring rescue ('safety') glucose-lowering treatment despite FMT or placebo."}
• {"endpoint_text":"- Describe how long the FMT effects last (i.e. time with 1st HbA1c at least 0.15% lower than baseline value)","definition_or_measurement_approach":"Duration (time) during which first HbA1c remains at least 0.15% lower than baseline; time-to-event/period measurement."}
• {"endpoint_text":"- Describe how many FMT cures are needed to obtain the primary end-point (-0.75% reduction of Hba1c)","definition_or_measurement_approach":"Count the number of FMT treatments required to achieve primary endpoint (−0.75% HbA1c reduction)."}
• {"endpoint_text":"- Evaluate the proportion of good responders’ patients (Good responders are defined in the protocol)","definition_or_measurement_approach":"Proportion of 'good responders' as defined in the protocol; definition details in protocol."}
• {"endpoint_text":"- Identify characteristics of good response related to the receiver (more detail in protocol)","definition_or_measurement_approach":"Characterisation of receiver-related factors associated with good response (clinical, metabolomic, bacterial diversity/composition); details in protocol."}
• {"endpoint_text":"- Identify characteristics of good response related to good donor’s (i.e. factors from the donor associated with good response in the receiver)","definition_or_measurement_approach":"Identify donor factors associated with good response in receivers; details in protocol."}
• {"endpoint_text":"- Identify gut microbiota signature (i.e. dominant/subdominant bacteria/taxa/ genus/ species) associated with good response of FMT, in the receiver post-FMT (at 6 and 12W) (metagenomic analysis as described above)","definition_or_measurement_approach":"Metagenomic analysis of receiver stool at 6 and 12 weeks to identify dominant/subdominant taxa associated with response."}
• {"endpoint_text":"- Changes in gut microbiota MGR and microbiota composition in receivers from baseline to 6, 18 and 24W follow-up (with further comparison between good/bad responders)","definition_or_measurement_approach":"Microbiota diversity and composition changes measured at baseline, 6, 18 and 24 weeks; subgroup comparison between responders and non-responders."}
• {"endpoint_text":"- Changes in systemic gut microbiota related metabolites (LC-MS metabolomics) from baseline to 6, 18 and 24W)","definition_or_measurement_approach":"LC-MS metabolomics of systemic samples at baseline, 6, 18 and 24 weeks to assess metabolite changes."}
• {"endpoint_text":"- Evaluate FMT safety (more detail in protocol)","definition_or_measurement_approach":"Safety evaluation per protocol (adverse events, serious adverse events etc.); details in protocol."}
• {"endpoint_text":"- Evaluate changes in quality of life after capsulized FMT (baseline vs. after FMT and between treatment groups using SF36 questionnaire)","definition_or_measurement_approach":"SF-36 questionnaire administered at baseline and post-FMT; compare within and between groups."}

France

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

06-11-2024

Processing Time Days

13

Number Of Sites

2

Number Of Participants

94

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévention","duties_or_roles":"Monetary support / funding","organisation_type":""}