Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): protocol for a 12-month randomised double-blind placebo-controlled trial.

INTRODUCTION: The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial. METHODS AND ANALYSIS: This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT). Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study. ETHICS AND DISSEMINATION: The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019. Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls. TRIAL REGISTRATION NUMBER: NCT03691987.

Randomised, placebo-controlled, double-blinded trial of fecal microbiota transplantation in severe obesity: a study protocol.

INTRODUCTION: Obesity is one of the main threats to public health in western countries and increases the risk of several diseases, overall morbidity and mortality. Sustained weight loss will reduce risk factors and improve several obesity comorbidities. Options are conservative treatment such as lifestyle changes, bariatric surgery or medications. Conservative treatment has a low success rate, and bariatric surgery is typically not reversible, with the risk of complications and recurrences. Treatment of obesity with medications has in recent years shown great promise, but the side effects are many, and the long-term effect is unknown. There is also a need for an option for patients where surgery has contraindications and conservative follow-up does not succeed.The research on obesity and gut microbiota has yielded promising results regarding weight reduction and metabolic health, but more research is needed to better understand the relationship between gut microbiota and severe obesity. This study could show proof of concept that gut microbiota from a lean donor could, in addition to lifestyle intervention, contribute to weight reduction in people suffering from severe obesity. METHOD AND ANALYSIS: This study aims to investigate if a fecal microbiota transplantation (FMT) from a lean donor leads to weight reduction in participants suffering from severe obesity. The study is a single-centre, double-blinded, placebo-controlled, parallel-group study with 60 participants. Participants will be randomised 1:1 for FMT from a lean donor or placebo. FMT or placebo will be delivered once by enema.We will include participants from the outpatient clinic for severe obesity, at the Medical Department, University Hospital of North Norway, Harstad, by invitation only. The study has a follow-up period of 12 months, with study visits of 3, 6 and 12 months post FMT. The primary endpoint is a weight reduction of ≥10%, 12 months after intervention.The results of the study will be published in open access journals. At the end of the study, the participants will receive information on which treatment group they belong to. ETHICS AND DISSEMINATION: The Regional Ethical Committee in North Norway (REK) approved the study protocol (2017/1655/REK Nord). We plan to present the results from the study at (inter)national conferences and publish in open-access general peer-reviewed journals. The enema method for FMT administration used in this study was developed by our study team. TRIAL REGISTRATION NUMBER: NCT03273855.

Colonic distribution of FMT by different enema procedures compared to colonoscopy - proof of concept study using contrast fluid.

BACKGROUND: Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent Clostridioides difficile infections and is under investigation as a treatment for several other diseases. FMT's mechanism of action is assumed to be through alterations of the colon microbiota. FMT can be delivered by several methods, but few studies have directly compared how FMT is distributed in the colon by different methods. Specifically, the proximal distribution of FMT delivered by enema is unknown. METHODS: In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema ÷) and after (enema +) the positioning procedure. CONCLUSION: Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema ÷). There were no adverse events. INTERPRETATION: This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021).