Donor Versus Autologous Fecal Microbiota Transplantation for Irritable Bowel Syndrome
Donor Versus Autologous Fecal Microbiota Transplantation for Irritable Bowel Syndrome
Many patients with irritable bowel syndrome (IBS) do not experience adequate symptom relief
 with current treatments. The pathophysiology of IBS is diverse, controversial and not
 completely understood. The next disruptive frontier would be to find a cure where the effect
 is predictable and lasting. The study groups phase 2 pilot trial was the first indication of
 a possible benefit from treating IBS with fecal microbiota transplantation (FMT) (Number
 needed to treat only five) (Fecal microbiota transplantation versus placebo for
 moderate-to-severe irritable bowel syndrome: a double-blind, randomized, placebo-controlled,
 parallel-group, single-centre trial he Lancet Gastroenterology and Hepatology 2018).
 Additional results from the same trial show that the treatment response may be predicted
 (unpublished data), and that the pathophysiologic mechanisms behind the treatment response
 also can be identified (Effects of fecal microbiota transplantation in subjects with
 irritable bowel syndrome are mirrored by changes in gut microbiome, Gut Microbes 2020). This
 study is the first phase 3 trial of FMT for IBS worldwide.

 The hypothesis of the trial is that donor FMT is more effective than placebo FMT in treating
 IBS, with little adverse events or complications. Patients ≥18 years with IBS are enrolled at
 five Norwegian Hospitals in this double blind randomized, placebo controlled, parallell-group
 multi center trial. Participants are randomized to FMT from a healthy donor (intervention
 group), or their own feces (placebo group). The primary outcome is the proportion of patients
 with ≥75 points decrease in the Irritable bowel Symptom Severity score 90 days after
 treatment.
Inclusion Criteria:

 Determined by participant medical history

 -  Diagnosed with IBS in the primary or secondary health care service

 -  IBS defined by the Rome IV criteria:

 -  Recurrent abdominal pain, on average at least 1 day per week during the previous
 3 months, that is associated with two or more of the following: 1)Defecation,
 either increased pain or pain releif. 2)Change in stool frequency 3)Change in
 stool form (appearance)

 -  Moderate to severe IBS symptoms, as defined by a score of ≥175 on the IBS-SSS

 -  All participants >50 years

 -  Colonoscopy within the last 5 years prior to study entry including negative
 mucosal biopsy for microscopic colitis in participants subtyped as IBS-D

 -  No planned evaluations or examinations for bowel related complaints

 -  No presence of:

 -  Malignant disease (excluding basalioma)

 -  Systemic disease including morbidly obesity (BMI ≥35), severe autoimmune disease
 or severe immune deficiency (acquired, congenital or due to medication)

 -  No history of:

 -  Severe psychiatric disorder, alcohol or drug abuse

 -  Inflammatory bowel disease, microscopic colitis, diverticulitis or ileus

 -  Abdominal surgery, with the exception of appendectomy, cholecystectomy, caesarean
 section and hysterectomy

 -  No "red flags'' indicating severe undiagnosed disease:

 -  Night sweats (Repeated episodes of extreme perspiration that may soak
 nightclothes or bedding)

 -  Unintentional weight loss (≥ 4.5 kilograms, or 5% of normal body weight) over
 less than 12 months without knowing the reason

 -  Blood in stool

 -  No family history of GI cancer defined as two or more first- or second-degree
 relatives, with:

 -  ≥ 1 diagnosed by age 50, OR

 -  ≥ 3 first- or second-degree relatives with GI cancer diagnosis, independent of
 age

 -  No use during previous 4 weeks:

 -  Drugs with analgesic action or with specific effects on bowel function.
 Participants are allowed to use Paracetamol, Non Steroid Anti-Inflammatory Drugs,
 and rescue medication, such as Polyethylene glycol (Laxabon, Movieprep, Movicol)
 or Loperamide

 -  No daily use of proton pump inhibitors or other antacids

 -  No introduction of antidepressants the last 12 weeks. Patients on a stable dose >12
 weeks are eligible.

 -  No treatment with antibiotics 12 weeks prior to study entry.

 -  No use of kolestyramin for bile acid malabsorption

 -  Not pregnant, lactating or planning pregnancy.

 -  No contraindications for rectal catheter insertion (including known damage to pelvic
 floor, sphincter or the pudendal nerve).

 -  Ability to comply with protocol requirements (including biobank participation).

 Determined by physical exam blood and stool tests

 -  Physical exam that does not indicate undiagnosed malignant, autoimmune, or infectious
 disease

 -  Laboratory work that does not indicate undiagnosed digestive, malignant, autoimmune,
 or infectious disease. The work up includes:

 -  Full blood count

 -  Erythrocyte sedimentation rate (ESR)

 -  C-reactive protein

 -  Anti-tissue transglutaminase IgA, total IgA

 -  Lactose genotype

 -  Stool tests for occult blood (Hemofec©), fecal calprotectin.

 -  Only if indicated by the patient history (i.e. travelers diarrhea)

 -  Stool test for fecal ova and parasite, Clostridoides difficile toxin and
 pathogenic bacteria (Shigella spp, Salmonella spp. Campylobacter spp, Yersinia
 spp, and toxin-producing Clostridoides difficile.) All test results must be
 negative.