Donor Versus Autologous Fecal Microbiota Transplantation for Irritable Bowel Syndrome

NCT04691544 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 183984
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

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 Additional results from the same trial show that the treatment response may be predicted (unpublished data), and that the pathophysiologic mechanisms behind the treatment response also can be identified (Effects of fecal microbiota transplantation in subjects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

Keywords

fecal microbiota therapy; bacteriotherapy; stool transplant; IBS; FMT; gut microbiota brain axis; functional disorder; IBS-M; IBS-D; IBS-C

Outcome Measures

Primary Outcomes (1)

• Proportion in the donorFMT (dFMT) versus autologousFMT (aFMT) group with ≥75 points decrease in the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) day 90 after treatment when compared to the score 8 days before treatment

  Scores on the IBS-SSS can range from 0 to 500 with higher scores indicating more severe symptoms. The IBS-SSS has five items. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (\>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement.

  Day 90 after treatment

Secondary Outcomes (15)

• Proportion in dFMT versus aFMT group with ≥75 points decrease in the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) day 365 after treatment when compared to the score 8 days before treatment

  Day 365 after treatment

• Proportion of patients in dFMT versus aFMT group with a ≥14 points increase in the IBS-Qualiy of Life (IBS-QoL) day 90 after treatment when compared to the score 8 days before treatment

  Day 90 after treatment

• Proportion in the dFMT vs aFMT group with 2 or more weeks with treatment success in Adequate relief by the Global Improvement Scale and Abdominal pain day 69, 76, 83 and 90 after treatment. For treatment success criteria A. and B. have to be fulfilled

  Day 69, 76, 83 and 90 after treatment

• Proportion of adverse events and serious adverse events in the dFMT versus aFMT group from treatment and until day 90 after treatment

  Day 90 after treatment

• Proportion of adverse events and serious adverse events in the dFMT versus aFMT group from treatment and until day 90 after treatment

  Day 365 after treatment

Other Outcomes (2)

• Changes in taxonomy and function of the microbiome, the immune system, metabolome and gut epithelial barrier in participants with vs without treatment success to dFMT and aFMT from before and until after treatment.

  8 days before treatment and until 90 and 365 days after treatment

• Differences in taxonomy and function of the microbiome, the immune system, metabolome and gut epithelial barrier before treatment in FMT donors vs participants with vs without treatment success to dFMT and aFMT from before and until after treatment.

  8 days before treatment and until 90 and 365 days after treatment

Study Arms (4)

Fecal microbiota transplant from donor A

ACTIVE COMPARATOR

One FMT delivered by enema

Biological: Fecal microbiota transplantation (FMT)

Fecal microbiota transplant from donor B

ACTIVE COMPARATOR

One FMT delivered by enema

Biological: Fecal microbiota transplantation (FMT)

Fecal microbiota transplant from donor C

ACTIVE COMPARATOR

One FMT delivered by enema

Biological: Fecal microbiota transplantation (FMT)

Fecal microbiota transplant from autologous feces

PLACEBO COMPARATOR

One FMT delivered by enema

Biological: Fecal microbiota transplantation (FMT)

Interventions

Fecal microbiota transplantation (FMT) BIOLOGICAL

Delivered by enema

Fecal microbiota transplant from autologous feces; Fecal microbiota transplant from donor A; Fecal microbiota transplant from donor B; Fecal microbiota transplant from donor C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• University Hospital of North Norway: lead
• Oslo University Hospital: collaborator
• Sorlandet Hospital HF: collaborator
• Haukeland University Hospital: collaborator
• Alesund Hospital: collaborator

Study Sites (1)

Ålesund Hospital

Ålesund, Norway

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Peter H Johnsen, MD PhD

  Univeristy Hospital of North Norway

  PRINCIPAL INVESTIGATOR

• Rasmus Goll, MD PhD

  University Hospital of North Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Triple blind randomized, placebo controlled, parallell-group multi center trial

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 31, 2020
• Study Start: May 5, 2021
• Primary Completion: September 1, 2023
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

NO (1)