Transplantation of Anaerobic Cultured Human Intestinal Microbiota in Irritable Bowel Syndrome (ACHIM2)

Patients with irritable bowel syndrome (IBS) are treated with microbiota from a human intestinal anaerobic sample cultured for decades. Patients are recruited consecutively with symptoms of IBS and serve as their own controls. After an observation time of 4 weeks, patients are recruited for a 1-week run-in and then given the cultured fecal microbiota by the duodenal route via gastroscopy. Two treatments are given within a 1-week interval. Assessment of symptoms are made before and 4 weeks after the last treatment (at 6 weeks). Additionally, fecal samples are collected for bacterial 16S ribosomal ribonucleic acid (rRNA) analysis and bacterial functional parameters (microflora-associated characteristics).

Study Overview

• Status: Unknown
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Biological: ACHIM

Detailed Description

Diarrhea-dominated irritable bowel syndrome (IBS-D) is studied in subjects by treatment with an anaerobic human intestinal microbiota cultured for 15 years and quality controlled with a specified content of bacterial species regularly over the years. Inclusion criteria is: Diarrheal disease since at least 4 weeks, 18-80 years of age, previously unsuccessful treatment with no symptomatic relief of antidiarrheals or resins, and signed informed consent.

Primary outcome was irritable bowel syndrome-symptom severity scale (IBS-SSS). Secondary outcome was Bristol stool scale (BSS).

Secondary outcome: Changes in fecal microflora distribution and multiplicity as shown by the 16S ribosomal ribonucleic acid (rRNA) analysis of feces.

Once eligible for the study, patients were monitored for a run-in period of one week with the IBS-SSS and the BSS plus fecal samples for analysis of bacterial species using the bacterial specific 16S rRNA differentiation.

Then, the anaerobic cultured human intestinal microflora (ACHIM) was given twice with an interval of 1 week. Thereafter, patients were further monitored over 4 weeks as regards IBS-SSS and BSS. Another feces sample was also collected for bacterial 16S rRNA analysis to evaluate the microbiota diversity.

The study will be evaluated using eligible subjects as their own controls by means of Wilcoxon's matched-pairs test, alternatively t-test for matched pairs.

Power analysis show that 40 subjects are needed to study in order to achieve a power of 80%.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peter Benno, MD, PhD; Phone Number: +46 705795554; Email: Peter.Benno@endoskopienheten.se
• Study Contact Backup: Name: Per Hellström, MD, PhD; Phone Number: +46 70 3727423; Email: Per.Hellstrom@medsci.uu.se

Study Locations

• Sweden
  • Stockholm, Sweden, 11157
    • Recruiting
    • Mag-tarm/endoskopienheten Hötorget
    • Contact: Peter Benno, MD, PhD; Phone Number: +46 7055795554; Email: Peter.Benno@endoskopienheten.se
    • Contact: Per Hellström, MD; PhD; Phone Number: +46 70 3727423; Email: Per.Hellstrom@medsci.uu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• IBS according to the Rome III criteria

Exclusion Criteria:

• Pregnancy
• Antibiotic and probiotics within 8 weeks before inclusion
• Unable to give informed consent
• Immunodeficiency (drug- och disease-related)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; Only one treatment arm. Patients are allocated under disease condition and later treated with ACHIM. The post-treatment disease progression is monitored.	Biological: ACHIM; After an observation period of 4 weeks patients with IBS-D will be treated with ACHIM; Other Names: Anaerobic cultured human intestinal microbiota

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Symptom relief according to irritable bowel syndrome-symptom severity scale (IBS-SSS)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential bacterial species population as defined by 16S RNA	Description of different bacterial species harboring in fecal samples before and after treatment with ACHIM. Exploratory outcome measure.	4 weeks
Normalization of stool consistency as determined by the Bristol stool scale	Normalization as determined by the Bristol stool scale	4 weeks

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Karolinska Institutet
• Investigators: Study Director: Per Hellström, MD, PhD, Uppsala University

Publications and helpful links

General Publications

• Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
• Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997 Sep;32(9):920-4. doi: 10.3109/00365529709011203.
• Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013 Nov;145(5):946-53. doi: 10.1053/j.gastro.2013.08.058. Epub 2013 Sep 7.
• Benno P, Norin E, Midtvedt T, Hellstrom PM. Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS. Best Pract Res Clin Gastroenterol. 2019 Jun-Aug;40-41:101607. doi: 10.1016/j.bpg.2019.03.003. Epub 2019 Apr 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: July 26, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: IBS; Microbiota
• 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: ACHIM2

Plan for Individual participant data (IPD)

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