The Role of Donor Selection on the Outcome of Faecal Microbiota Transplantation in Patients With Irritable Bowel Syndrome

The Role of Donor Selection on the Outcome of Faecal Microbiota Transplantation (FMT) in Patients With Irritable Bowel Syndrome: a Randomised, Placebo-controlled Study

Two hundred patients are randomized 1:1:1:1 into placebo (own feces), or receiving 90 g fecal transplant from donor A, donor B or donor C. The fecal transplant is administered to the distal duodenum via the working channel of a gastroscope. The patients shall complete 6 questionnaires measuring symptoms, fatigue, quality of life, stool form and diet intake at the baseline and at the end point of the trial and provide a feces sample at the baseline, and at 3, 6 and 12 months after FMT. Dysbiosis and fecal bacterial profile are determined by using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9.

Study Overview

• Status: Not yet recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Dietary supplement: Faeces

Detailed Description

Study Description Brief Summary: Two hundred patients are randomized1:1:1:1 into placebo (own feces), receiving 90 g fecal transplant from donor A, donor B or donor C. The fecal transplant is administered to distal duodenum via working channel of a gastroscope. The patients shall complete 5 questionnaires measuring symptoms, fatigue, quality of life and diet intake at the baseline and at the end point of the trial and provid 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 PCR DNA amplification/probe hybridization covering regions V3-V9.

Detailed Description: Patients: Two hundred patients who fulfil Rome IV criteria for irritable bowel syndrome (IBS) shall be included in the study. All IBS subtypes shall be included with the exception of IBS-U. Donors: The investigators have selected 3 donors (A, B and C) according to the criteria used in their previous randomised double-blind, placebo-controlled study. These criteria included: being a healthy man or woman with no history of disease and no use of medications, aged 20-50 years, being a non-smoker, and exercising regularly. They were borne by vaginal delivery and breastfed. They were treated only a few times with antibiotics during their life. They are screened according to the European guidelines for donors for FMT. Before they are accepted as donors, the bacterial profile and dysbiosis were analysed in a faecal sample using the GA-map dysbiosis test, with a dysbiosis index (DI)= 1, indicating normobiosysis. Their feces shall be tested every third month during the trial to exclude communicable disease. Donor A is a male aged 41 years, donor B is a female aged 31 and donor C is a male aged 35.

Protocol: The patients are randomized 1:1:1:1 into placebo (to receive their own feces), to receive 90 g fecal transplant from donor A, from donor B or donor C. Fecal transplant is administered to the distal duodenum via the working channel of a gastroscope. The patients shall complete 5 questionnaires and deliver fecal samples at the baseline, and at 3 , 6 , and 12 months after FMT. Feces collection, preparation and administration: Faeces from both the donors and patients shall be collected and stored at - 80ºC. Frozen donor faeces shall be thawed in the refrigerator at 4ºC, and each 30 g portion is dissolved in 30 mL of 4ºC cold 0.9% sterile saline. The dissolved stool is administrated to the patients, after overnight fast, through the working channel of a gastroduodenoscope in the pars descendens of the duodenum always distal to the papilla of Vater. Questionnaires

1. IBS Symptom Severity Scale (IBS-SSS).
2. Birmingham Symptom Scale.
3. Fatigue Assessment Scale (FAS).
4. IBS-quality of life (IBSQoL) Questionnaire.
5. Semi-quantitive Food Frequency Questionnaire (FFQ)
6. Bristol Stool Form Scale

Bacterial analysis: Fecal bacterial analysis is performed using a 16S rRNA gene PCR DNA amplification/probe hybridization technique covering regions V3-V9. DNA extraction is done by 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). Fourty-nine bacterial probes are species specific, 19 detect bacteria at the 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 (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan G Hatlebakk, PhD; Phone Number: +47 97707817; Email: jhat@helse-bergen.no
• Study Contact Backup: Name: Magdy El-Salhy, PhD; Phone Number: +4747270376; Email: magdy.elsalhy@sklbb.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who fulfil Rome IV criteria for the

diagnosis of IBS.

• Patients were investigated to exclude other

gastrointestinal organic cause(s).

• Moderate-to-severe IBS symptoms, as indicated

by a score of ≥175 on the IBS-SSS questionnaire

Exclusion Criteria:

• Pregnant, women planning pregnancy or lactating women.
• The use of antibiotics or probiotics within 1

month prior to FMT.

• Having undergone any abdominal surgery, with

the exception of appendectomy, cholecystectomy,

caesarean section and hysterectomy.

• Previous treatment with FMT.
• Immunocompromised patients including those being

treated by immunosuppressive medications.

• Patients with co-morbidity such as kidney failure,

diabetes or chronic heart disease.

• Patients with serious psychiatric disorders

or alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Own faeces instilled to the small intestine during gastroscopy	Dietary supplement: Faeces; Faeces from donor selected based on European guidelines, compared to own faeces (placebo)
Experimental: Arm A; 90g of faeces from Donor A is instilled to the small intestine during gastroscopy	Dietary supplement: Faeces; Faeces from donor selected based on European guidelines, compared to own faeces (placebo)
Experimental: Arm B; 90g of faeces from Donor B is instilled to the small intestine during gastroscopy	Dietary supplement: Faeces; Faeces from donor selected based on European guidelines, compared to own faeces (placebo)
Experimental: Arm C; 90g of faeces from Donor C is instilled to the small intestine during gastroscopy	Dietary supplement: Faeces; Faeces from donor selected based on European guidelines, compared to own faeces (placebo)

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 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: Haukeland University Hospital
• Collaborators: University of Bergen
• Investigators: Study Chair: Jan G Hatlebakk, PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 2, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Estimated): December 14, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: November 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: 630339

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the completion of the study, study data may be made available to other researchers after contacting the primary investigator
• IPD Sharing Time Frame: After completion of the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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