FAIS trial; Faecal transplantation in Adolescents with refractory Irritable bowel Syndrome

Patients

• 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

o Before inclusion, all patients undergo routine laboratory testing to exclude underlying organic disorders:
complete blood cell count, C-reactive protein, celiac screening (anti-transglutaminase antibodies and IgA), and faecal calprotectin. The need for further diagnostic testing is left to the discretion of the treating physician.

• 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)



Donors

• Age ≥18 years

• Non-smokers

• Ability to give informed consent

• BMI 18-25 kg/m2

• Regular stool pattern

Patients

• Current treatment by another health care professional for abdominal symptoms

• Known concomitant organic gastrointestinal disease

• Known diagnosis of inflammatory bowel disease (i.e. Crohn’s 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

o For example: HIV, infectious diseases leading to immunosuppression, bone marrow malignancies

o Use of systematic chemotherapy

• Life expectancy < 12 months

• Use of concomitant medication, including proton pomp inhibitors (PPI), with the exception of pain medication

o 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:

o Hemicolectomy (defined as: surgery resulting in a resection of > 0.5 of the colon)

o Presence of a pouch due to surgery

o 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



Donors

• 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 (Crohn’s 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:

o 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)

o Viruses (faecal PCR-test)

 Norovirus Type I and II, Astrovirus, Sapovirus, Adenovirus type 40/41, Rotavirus, Enterovirus, Adenovirus non-41/41

o Parasites:

 Giardia lamblia, Cryptosporidium spp., Entamoeba histolytica, Dientamoeba fragilis, Microsporidium spp., Blastocystis hominis, Isospora spp.

 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 Jacob’s disease

• History of current use of IV drugs

• History of treatment with growth factors

• Untreated infection with: Treponematoses, TBC, Herpes virus