Donor Versus Autologous Fecal Microbiota Transplantation for Irritable Bowel Syndrome

NCT ID: NCT04691544

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 450 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-05
• Study Completion Date: 2026-12-31

Brief Summary

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 Additional results from the same trial show that the treatment response may be predicted (unpublished data), and that the pathophysiologic mechanisms behind the treatment response also can be identified (Effects of fecal microbiota transplantation in subjects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.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Fecal microbiota transplant from donor A

One FMT delivered by enema

Group Type: ACTIVE_COMPARATOR

Fecal microbiota transplantation (FMT)

Intervention Type: BIOLOGICAL

Delivered by enema

Fecal microbiota transplant from donor B

One FMT delivered by enema

Group Type: ACTIVE_COMPARATOR

Fecal microbiota transplantation (FMT)

Intervention Type: BIOLOGICAL

Delivered by enema

Fecal microbiota transplant from donor C

One FMT delivered by enema

Group Type: ACTIVE_COMPARATOR

Fecal microbiota transplantation (FMT)

Intervention Type: BIOLOGICAL

Delivered by enema

Fecal microbiota transplant from autologous feces

One FMT delivered by enema

Group Type: PLACEBO_COMPARATOR

Fecal microbiota transplantation (FMT)

Intervention Type: BIOLOGICAL

Delivered by enema

Interventions

Fecal microbiota transplantation (FMT)

Delivered by enema

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Diagnosed with IBS in the primary or secondary health care service
• Aged 18-65 years with IBS defined by the Rome IV criteria:
• 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

Exclusion

• Planned evaluations or examinations for bowel related complaints
• Known presence of:

• Endometriosis or polycystic ovarian syndrome
• Diabetes type 1 and 2
• Systemic disease including
• Morbidly obesity (BMI ≥35)
• Severe autoimmune disease
• Severe immune deficiency (acquired, congenital or due to medication)
• Previous treatment with FMT
• History of:

• Severe psychiatric disorder, alcohol or drug abuse. Mood disorders are allowed as long as there is no reason to believe that it will interfere with the ability to participate in the study.
• Inflammatory bowel disease, microscopic colitis, diverticulitis or ileus
• Abdominal surgery, with the exception of appendectomy, cholecystectomy, caesarean section and hysterectomy
• Malignant disease (excluding basalioma)
• "Red flags'' indicating severe undiagnosed disease including:

• 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
• 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
• Use of the following the previous 4 weeks:

• Drugs with effects on bowel function..Rescue medication, such as Polyethylene glycol (Laxabon, Movieprep, Movicol) or Loperamide is allowed
• Drugs with analgesic action. Use of paracetamol, Non.Steroid Anti-Inflammatory Drugs ≤3 days week is allowed.
• Use of proton pump inhibitors or other antacids ≥3 days week
• Introduction of antidepressants or anxiolytics the last 12 weeks. Patients on a stable dose >12 weeks are eligible.
• Treatment with antibiotics 12 weeks prior to study entry.
• Use of kolestyramin for bile acid malabsorption
• Pregnant, lactating or planning pregnancy.
• Physical exam indicating undiagnosed malignant, autoimmune, or infectious disease
• Laboratory work up indicating undiagnosed digestive, malignant, autoimmune, infectious disease or alternative diagnosis to the IBS related signs and symptoms. The work up includes:

• Full blood count
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein
• Anti-tissue transglutaminase IgA, total IgA
• Lactase genotype
• Stool tests for:
• Occult blood (Hemofec©).
• Fecal calprotectin indicating inflammatory bowel disease. The detection limit that excludes participants will depend on which assays is used for analysis at the different study centers.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Sorlandet Hospital HF

OTHER_GOV

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

Alesund Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter H Johnsen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Univeristy Hospital of North Norway

Rasmus Goll, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of North Norway

Locations

Ålesund Hospital

Ålesund, , Norway

Countries

Norway

Other Identifiers

183984

Identifier Type: -

Identifier Source: org_study_id