Faecal Microbiota Transplantation (FMT) in Patients With IBSmechanism(s) of Action

Faecal Microbiota Transplantation (FMT) in Patients With Irritable Bowel Syndrome (IBS): Optimizing the Treatment and Its Mechanism(s) of Action

Two hundrad patients are randomized to either 90 g transplant, 90 g transplant twice with 1week interval into the distal small intestine via working channel of a gastroscope, or to 90 g transplant into the coecum of the colon via working channel of a colonoscope. The patients shall complete 5 questionnaires measuring symptoms, fatigue and quality of life and collect a feces sample at the baseline, and at 3, 6 and 12 months after FMT. Dysbiosis and fecal bacterial are determined by using 16S rRNA gene.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Dietary supplement: Feces

Detailed Description

Patients Two hundrad patients who fulfil Rome IV criteria for irritable bowel syndrome (IBS) shall be included in the study. All the IBS subtypes shall be included.

Donor Investigators are going to use the same super-donor they used in their previous randomised double-blind, placebo-controlled study. The donor is athletic Caucasian man aging 36 years. He is non-smoker and is completely healthy without any medication and with a BMI of 23.5. He is not relative to any of the patients in the trial. He was borne by vaginal delivery and breastfeed. He was treated 3 times with antibiotics during his life. He trains 5 times weekly an hour each time. He took regularly dietary supplements rich in proteins, vitamins, fibres and minerals that made his diet richer than average in these substances. He was screened according to the guidelines for donors for FMT. Before he was accepted as a donor the microbiota was analysed in a faecal sample using GA-map Dysbiosis test. The analysis revealed a dysbiosis index (DI)= 1, indicating normobiosysis. In addition, he had excess of bacteria belonging to the Firmicutes. His faeces shall be tested every third moth during the trial.

Protocol

The patients are randomized to either 90 g transplant, 90 g transplant twice with 1week interval into the distal small intestine, or to 90 g transplant into the coecum of the colon. The patients shall complete 5 questionnaires and deliver fecal samples at the baseline, and at 3 , 6 , and 12 months after FMT.

Faeces collection, preparation and administration Faeces from both the donor and patients shall be collected and stored at - 80•. Frozen faeces shall be thawed and each 30 g is dissolved in 30 mL of 0.9% sterile saline. The dissolved stool administrated to the patients, after overnight fast, through working channel of gastroduodeno-scope in pars descendent duodenum distal to the papilla of Vater or to the coecum through working channel of a colonoscope.

Analysis Questionnaires

1. IBS symptom severity Scale (IBS-SSS).
2. Birmingham Symptom scale.
3. IBS-quality of life (IBSQo) Questionnaire.
4. Short form of Nepean Dyspepsia Index (SF-NDI).
5. Fatigue Assessment Scale (FAS).

Microbiome analysis Gut microbiota analysis is performed using the Genetic analysis-mapTM Dysbiosis test (Genetic Analysis AS, Oslo, Norway) by algorithmically assessing faecal bacterial abundance and profile (dysbiosis index, DI), and potential deviation in the microbiome from normobiosis. GA-map test is based on faecal homogenization, mechanical bacterial cell disruption and automated total bacterial genomic DNA extraction using magnetic beads. DI is based on 54 DNA probes targeting more than 300 bacterial strains based on their 16S rRNA sequence in seven variable regions (V3-V9). Twenty-six bacteria probes are species specific, 19 detect bacteria on genus level, and 9 probes detect bacteria at higher taxonomic levels. Probe labelling is by single nucleotide extension and hybridization to complementary probes coupled to magnetic beads, and signal detection by using BioCode 1000A 128-Plex Analyser (Applied BioCode, Santa Fe Springs, CA, USA). A DI above 2 shows a microbiota profile that differs from that of the normobiotic reference collection (DI 1-2: non-dysbiosis, DI: moderate, DI 4-5: severe dysbiosis).

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Haugesund, Norway, 5504
    • Helse Fonna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who fulfil Rome IV criteria for the diagnosis of IBS.
2. Patients were investigated to exclude other gastrointestinal organic cause(s).
3. Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity Scoring System (IBS-SSS).

Exclusion Criteria:

1. Pregnant or lactating women.
2. The use of antibiotics or probiotics within 1 month prior to FMT.
3. Immunocompromised patients defined as those treated by immune- suppressive medications.
4. Patients with co-morbidity such as kidney failure or chronic heart disease.
5. System disease such as diabetes.
6. Patients with serious psychiatric disorders or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Smal intestine once; 90-g fecal transplant given into the small intestine once.	Dietary supplement: Feces; Feces from healthy donor
Active Comparator: Small intestine twice; 90-g fecal transplant given into the small intestine twice with 1 week interval.	Dietary supplement: Feces; Feces from healthy donor
Active Comparator: Large intestine once; 90-g fecal transplant given into the large intestine once.	Dietary supplement: Feces; Feces from healthy donor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IBS-SSS total score	Irritable bowel syndrome-symptom severity score (IBS-SSS) is a visual analogue scale questionnaire with a maximum score of 500 points. A decrease in total score by ≥50 points is considered as a response.	12 months after FMT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Dysbiosis index	Dysbiosis index (DI) is a 5 -scale index. A DI above 2 shows a microbiota profile that differs from that of the normobiotic reference collection (DI 1-2: non-dysbiosis, DI 3: moderate, DI 4-5: severe dysbiosis)	12 months after FMT

Collaborators and Investigators

• Sponsor: Helse Fonna
• Collaborators: University of Bergen
• Investigators: Study Chair: Magdy El-Salhy, MD,PhD, Helse Fonna

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): March 25, 2022

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Quality of life; Fatigue; Intestinal microbiota; Dysbiosis; Donor; Fecal microbiota transplantation; Abdominal symptom
• 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: Helse Fonna

Drug and device information, study documents

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