The Optimal Route of Fecal Microbiota Transplantation for Irritable Bowel Syndrome

The object of this study is to find out is there an optimal route for the fecal microbiata transplant (FMT) in patients that suffer from irritable bowel syndrome. The investigators compare outcomes in patients with repeated fecal microbiome samples and make symptomatic questionnaires (i.e. IBS-SSS, GSRS) to find out if there is difference in severity of symptoms compared to FMT given in duodenogastroscopy or in coloscopy.

Study Overview

• Status: Recruiting
• Conditions: IBS - Irritable Bowel Syndrome; Microbial Substitution
• Intervention / Treatment: Other: Fecal microbiota transplant or plasebo through endoscopy

Detailed Description

Irritable bowel syndrome (IBS) is a common functional disorder affecting approximately 10% globally.[1] It is often referred to as benign, although, when severe, may cause significant reduction of quality of life and work absenteeism. The etiology of IBS is unknown although many theories have been proposed. Altered gut motility, epithelial hyperpermeability, low grade inflammation, visceral hypersensitivity, epigenetics and genetics, altered gut-brain interaction and psychological stressors have all been reported in patients with IBS.

Several studies have detected alterations in the gut microbiota composition between IBS patients and healthy controls, however a microbiota typical for IBS patients has not been conclusively defined.

Fecal microbiota transplantation has over 90% efficace in recurrent Clostridioides difficile infection (rCDI), for which it has been in clinical use for a decade. FMT is currently recommended after the second relapse of rCDI. FMT is recommended to be considered only in clinical trial settings for other indications than rCDI.

Randomized controlled studies in FMT for IBS have conflicting results. In studies with a single administration of FMT in colonoscopy a mild transient reduction of IBS symptoms has followed the intervention. In studies with fecal capsules there has not been any benefit observed. FMT via gastroscopy exerted a clear benefit with an up to 89.1% response rate. These surprisingly good results were thought to be contributable to careful donor selection, however the study included only one donor and no specific characteristics of microbiota were indentified of the suspected superdonor. Although all these three administration routes altered the microbiota of IBS patients towards that of the donor, a concurrent decrease in the symptoms was observed only when FMT was administered via colonoscopy or gastroscopy.

Manipulation of microbiota through FMT remains to be potential treatment option for IBS, however, several mechanistic questions await answering. Investigators do not yet know what is the component of stool which would carry the healing potential. There needs to be further research to define optimal donors as well as optimal patients who would be prone to benefit of FMT. The amount and number of FMT treatments may be a factor contributing to the outcome.

It is also undefined in which extend does the route of administration of FMT contribute to the outcome in IBS patients. Therefore, the investigators present a placebo-controlled trial "the optimal route" to provide further mechanistic knowledge of the optimal FMT protocol in this patient group.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Teemu T Puodinketo, MD; Phone Number: +35823139427; Email: teemu.puodinketo@tyks.fi
• Study Contact Backup: Name: Kimmo Salminen, MD; Phone Number: +35823130691; Email: kimmo.salminen@tyks.fi

Study Locations

• Finland
  • Paijat-Hame
    • Lahti, Paijat-Hame, Finland, 15850
      • Recruiting
      • Central Hospital of Päijät-Häme
      • Contact: Perttu Lahtinen, MD; Email: perttu.lahtinen@phhyky.fi
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • Recruiting
      • Helsinki University Hospital
      • Contact: Perttu Arkkila, Professor; Email: perttu.arkkila@hus.fi
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland, 20520
      • Recruiting
      • Turku University Hospital
      • Contact: Kimmo Salminen, MD; Phone Number: +35823130691; Email: kimmo.salminen@tyks.fi
      • Contact: Teemu P Puodinketo, MD; Phone Number: +35823139427; Email: teemu.puodinketo@tyks.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult
• 18-70 years
• known of Finnish language
• IBS, (new or old diagnosis according to Roma III or IV criteria), all subtypes
• Informed consent
• Moderate to severe IBS symptoms, IBS-SSS > 175

Exclusion Criteria:

• Pregnancy
• Antibiotic or probiotic treatment, on-going or previous month
• Abuse of drugs, alcohol or medications
• Other diagnosis besides IBS causing the GI symptoms, such as IBD, microscopic colitis or bile acid diarrhea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FMT through colonoscopy; Patient gets FMT in ceacum and plasebo in duodenum.	Other: Fecal microbiota transplant or plasebo through endoscopy; Colonoscopy and gastroscopy
Active Comparator: FMT through duodenogastroscopy; Patient gets plasebo in ceacum and FMT in duodenum.	Other: Fecal microbiota transplant or plasebo through endoscopy; Colonoscopy and gastroscopy
Placebo Comparator: Plasebo; Patient gets plasebo in colonoscopy and in gastroscopy.	Other: Fecal microbiota transplant or plasebo through endoscopy; Colonoscopy and gastroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the different routes of FMT, for alteration of gut microbiota towards that of the donor.	The changes in the engraftment of specific bacteria between the active groups is of special interest, and the changes in the microbiota during the whole of study in the intervention group and in the plasebo group.	Microbiota is tested at prescreening visit, at the baseline and in 4, 12 and 52 weeks after FMT-procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main clinical outcome is reduction of abdominal pain three months after FMT.	Gut pain: "Has your abdominal pain reduced after the intervention? "Broadening of diet: "Have you been able expand your diet after the intervention?" Global IBS symptoms: "reduction of IBS-SSS total score 50 points or more from the baseline value"	3 months
GI Symptoms: THE GASTROINTESTINAL SYMPTOM RATING SCALE (GSRS)	Change in symptoms in GSRS questionnaire. Scale from 0 to 90, lower the score better the outcome.	in 3 months and in 1 year points compared to baseline.
Mood, General Anxiety-Disorder 7 - questionnaire	Mood changes in GAD -questionnaire. Aim is to lower the score in GAD-7 questionnaire.	The change in the score of questionnaires between the baseline at 3 months and 12 months
Mood, Beck's Depression Inventory.	Mood changes in BDI -questionnaire. Score from 0-60. Aiming to lower the score in BDI-questionnaire.	The change in the score of questionnaires between the baseline at 3 months and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events as assessed	Safety of FMT and endoscopic procedures, is there complications that need hospitalisation or other medical intervention for patients. Results given in numbers and differentiated between major and minor complications.	through study completion, an average of 1 year
Broadening of diet	D2D-questionnaire, that gives an overall index-value of how healthy subjects diet is, higher the value, healthier the diet.The D2D questionnaire gives on index-value from 0-100.	before intervention and after 3 months.

Collaborators and Investigators

• Sponsor: Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 17, 2022
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: IBS; FMT; microbiome; Fecal microbiota transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: T109/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No