The FAIS-Trial: Faecal Transplantation in Adolescents With Refractory Irritable Bowel Syndrome
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- The proportion of patients with > 50% reduction of their abdominal pain intensity and pain frequency at t=12 weeks after the first faecal transplantation
研究概览
简要总结
A Double-blind randomised placebo-controlled pilot study as well as a reversed translational part To investigate whether two faecal transplantations from either allogeneic (healthy) or autologous (own) donor, administered through a nasoduodenal tube, has beneficial effects on irritable bowel syndrome (IBS) symptoms such as abdominal pain frequency and severity. Secondary objective is to study microbiota changes in faeces samples.
详细描述
Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain or discomfort associated with a change in stool form or frequency, in the absence of a biochemical or structural explanation for these symptoms. The prevalence of IBS in the general adult population is 9.8-12.8%, which is in accordance to the prevalence of IBS in children and adolescents (6.2%-11.9%). Patients with IBS report a decreased quality of life, high work or school absence, and are more at risk than healthy controls of developing depressive and anxiety disorders. Consequently, the healthcare costs are substantial; annual costs of care for adults with IBS in the USA are estimated to be over $20 billion. Total annual costs per paediatric IBS patient in the Netherlands are estimated to be €2500. Although the pathophysiology of IBS has not been fully elucidated, pathophysiological abnormal gastrointestinal motility, visceral hypersensitivity, altered brain-gut function, low-grade inflammation, psychosocial disturbance and intestinal microbiota characteristics have been proposed to contribute to the pathophysiology. Current treatment focuses on abnormal gastrointestinal motility, altered brain-gut function and psychosocial disturbances. However, a significant amount of IBS patients has remaining symptoms, despite these treatment regimens. These patients are considered to be therapy-resistant, also called refractory. Treatment focusing on other components of the underlying pathophysiology, such as the intestinal microbiota, might therefore lead to new therapeutic successes in this group of patients. In this light, being able to modify the intestinal microbiota inrefractory IBS patients could have beneficial effects on symptoms. Faecal transplantation, a relatively new treatment regimen that enables the modification of the microbiome, has been shown to be highly effective in treating Clostridium difficile infections and also yielded promising results in patients with other diseases such as diabetes.
Objective
To investigate whether two faecal transplantations from either allogeneic (healthy) or autologous (own) donor, administered through a nasoduodenal tube, has beneficial effects on irritable bowel syndrome (IBS) symptoms such as abdominal pain frequency and severity. Secondary objective is to study microbiota changes in faeces samples.
Study design: Double-blind randomised placebo-controlled pilot study as well as a reversed translational part.
Study Population: Patients with refractory IBS, defined as a failure to improve after standard medical treatment, at least 6 sessions of a psychological therapy and absence of response to at least 1 pharmacological agent (aged 16-21 years, male/female, no concomitant medication, non-smoking), will be recruited by their (paediatric) gastroenterologist at the Academic Medical Centre (Amsterdam, the Netherlands) and patients from other hospitals will be enrolled. Donors: relatives or volunteers will serve as faeces donor, potential donors will be thoroughly screened.
Treatment: After bowel lavage with Klean-Prep, patients will be treated with faecal transplantation at t=0 and t=6 weeks, processed for duodenal tube infusion. Faeces will be collected from a healthy donor (allogeneic) as well as the patient him/herself (autologous), in which their own faeces will be used as a placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients will be randomised by a computerised random-number generator to one of the following two treatment arms:
- allogeneic faecal infusions at t=0 and t=6.
- autologous faecal infusions at t=0 and t=6.
Randomisation and preparation of the faeces will be performed by one of the research assistants. He/she is the only person who will know which treatment the patient will be given and will have no role in further parts of the study.
The randomisation list will be kept under secured access by the Clinical Research Unit of the AMC Amsterdam, who will perform the randomisation. In case of an emergency the study medication can be unblinded after consultation of the principal investigator.
入排标准
- 年龄范围
- 16 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 16-21 years
- •Non-smokers
- •Ability to give informed consent
- •Established irritable bowel syndrome diagnosis according to the Rome IV criteria for children or adults
- •According to a recently published guideline by the Rome Foundation for the design of pharmacological clinical trials in adolescents, patients are required to have an average daily pain rate of at least 30mm on the pain component scale of the IBS-SSS
- •Symptoms are present for ≥12 months
- •The patient has received adequate explanation and reassurance for his/her symptoms
- •Appropriate dietary interventions have occurred, including the normalisation of the insoluble fibre intake and a decrease in gas producing foods
- •Absence of response to a minimum of six sessions of psychological treatment (i.e. cognitive behavioural therapy and/or hypnotherapy)
- •Absence of response to an adequate dose of at least one IBS specific pharmacological agent tried for a minimum of 6 weeks (like Mebeverine or peppermint oil capsules)
- •Age ≥18 years
- •Non-smokers
- •Ability to give informed consent
- •BMI 18-25 kg/m2
- •Regular stool pattern
排除标准
- •Current treatment by another health care professional for abdominal symptoms
- •Known concomitant organic gastrointestinal disease
- •Known diagnosis of inflammatory bowel disease (i.e. Crohns disease or ulcerative colitis)
- •Known diagnosis of an autoimmune disease (e.g. hypo- or hyperthyroidism, celiac disease, rheumatoid arthritis)
- •Known diagnosis of cystic fibrosis
- •Known diagnosis of porphyria
- •Current use of drugs which influence gastrointestinal motility, such as erythromycin, azithromycin, butyl scopolamine, domperidone, peppermint oil capsules, and Iberogast
- •Known pregnancy or current lactation
- •Condition leading to profound immunosuppression (HIV, infectious diseases leading to immunosuppression, bone marrow malignancies/use of systematic chemotherapy)
- •Life expectancy < 12 months
- •Use of concomitant medication, including proton pomp inhibitors (PPI), with the exception of pain medication (pain medication in the form of Paracetamol or NSAIDs is allowed)
- •Use of systemic antibiotics in preceding 6 weeks
- •Use of probiotic treatment in preceding 6 weeks
- •Positive stool cultures for Clostridium difficile, Helicobacter pylori
- •Positive Dual Faeces Test for Giardia lamblia, Dientamoeba fragilis, Entamoeba histolytica
- •XTC, amphetamine or cocaine abuse
- •History of surgery (hemicolectomy (defined as: surgery resulting in a resection of > 0.5 of the colon), presence of a pouch due to surgery, presence of stoma)
- •Known intra-abdominal fistula
- •Vasopressive medication, ICU stay
- •Signs of ileus, diminished passage
- •Allergy to macrogol or substituents, e.g. peanuts, shellfish
- •Insufficient knowledge of the Dutch language
- •Abnormal bowel motions, abdominal complaints or symptoms indicative of irritable bowel syndrome
- •An extensive travel behaviour
- •Unsafe sex practice (questionnaire)
- •Use of any medication including PPI
- •Antibiotic treatment in the past 12 weeks
- •A positive history/clinical evidence for inflammatory bowel disease (Crohns disease or ulcerative colitis) or other gastrointestinal diseases, including chronic diarrhoea or chronic constipation
- •A positive history/clinical evidence for autoimmune disease (type 1 diabetes, Hashimoto hypothyroidism, Graves hyperthyroidism, rheumatoid arthritis, celiac disease) and/or patients receiving immunosuppressive medications
- •History of or present known malignant disease and/or patients who are receiving systemic anti-neoplastic agents
- •Known psychiatric disease (depression, schizophrenia, autism, Asperger's syndrome)
- •Known chronic neurological/neurodegenerative disease (e.g. Parkinson's disease, multiple sclerosis)
- •Predisposing factors for potential transmittable diseases (e.g. regular sexual contact with prostitutes/promiscuity)
- •Positive blood tests for the presence of: HIV, HTLV, lues, Strongyloides, amoebiasis
- •Active hepatitis A, B-, C- or E-virus infection or known exposure within recent 12 months, acute infection with cytomegalovirus (CMV) or Epstein-Barr virus (EBV)
- •Positive faecal tests for the presence of:
- •Bacteria (Clostridium difficile, Helicobacter pylori, Salmonella spp., Shigella spp., pathogenic Campylobacter spp., Yersinia enterocolitica, Aeromonas spp., Plesiomonas shigelloides, Antibiotic resistant bacteria: Extended spectrum beta-lactamase (ESBL)-producing Enterobactereacceae, VRE (vancomycin resistant enterococ)
- •Viruses (faecal PCR-test: Norovirus Type I and II, Astrovirus, Sapovirus, Adenovirus type 40/41, Rotavirus, Enterovirus, Adenovirus non-41/41)
- •Parasites (Giardia lamblia, Cryptosporidium spp., Entamoeba histolytica, Dientamoeba fragilis, Microsporidium spp., Blastocystis hominis, Isospora spp. Or more than 1 of the following non-pathogenic parasites: Entamoeba gingivalis, Entamoeba hartmanni, Entamoeba coli, Entamoeba polecki, Endolimax nana, Iodamoeba bütschlii, Entamoeba dispar, Entamoeba moshkovskii
- •If a donor turns out positive for only 1 of the above mentioned non-pathogenic parasites, inclusion is acceptable
- •o Parasitic worm eggs, larvae, protozoan cysts and oocysts
- •Chronic pain syndromes (e.g. fibromyalgia)
- •Major relevant allergies (e.g. food allergy, multiple allergies)
- •Recent (gastrointestinal) infection (within last 6 months)
- •Tattoo or body piercing placement within last 6 months
- •Known risk of Creutzfeldt Jacobs disease
- •History of current use of IV drugs
- •History of treatment with growth factors
- •Untreated infection with: Treponematoses, TBC, Herpes virus
结局指标
主要结局
The proportion of patients with > 50% reduction of their abdominal pain intensity and pain frequency at t=12 weeks after the first faecal transplantation
时间窗: T=12 weeks
This will be assessed with the pain component of the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) score. With 2 questions, the severity and frequency of the abdominal pain on the last 10 days is measured. The IBS-SSS is the only symptom severity scale that has been responsive to treatment effects. It has been recommended as the best instrument to obtain information on specific IBS related symptoms.
次要结局
- Intra-individual changes in faecal gut microbiota composition(At baseline, 6 weeks, 12 weeks, 6 months and 12 months after faecal transplantation)
- Absence of school or work, health care resources and costs(baseline, t=6 and t=12 weeks, and t=6 and 12 months.)
- Number of participants with treatment-related adverse events as assessed by CRP, liver profile and renal profile(t=0, t=6 and t=12 weeks)
- The proportion of patients with > 50% reduction of their abdominal pain intensity and pain frequency(At t=6 and t=12 months)
- Adverse events(At t=3, t=6, t=12 and t=16 weeks, and t=6 and 12 months)
- Total IBS-SSS score(At baseline, t=3, t=6, t=12 and t=16 weeks, and t=6 and 12 months)
- Adequate relief(t=6 and t=12 weeks, and t=6 and 12 months)
- Health related quality of life(baseline, t=6 and t=12 weeks, and t=6 and 12 months)
- Depression and anxiety(baseline, t=6 and t=12 weeks, and t=6 and 12 months.)
研究者
M.A. Benninga
Prof.dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)