Allogeneic Microbiota-reconstitution (AMR) in Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)

Diarrhea-predominant Irritable Bowel Syndrome Clinical Trial

— AMIRA  

Official title:

Allogeneic Microbiota-reconstitution (AMR) for the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome - the AMIRA Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04095988
• Other study ID #: AMIRA
• Secondary ID: 2016-002550-20
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2016
• Est. completion date: May 2021

Study information

• Verified date: January 2020
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will perform a multicenter, 2:1 randomized, double-blinded, placebo-controlled trial of AMR in patients with diarrhea predominant-IBS (IBS-D) diagnosed according to Rome III criteria and the IBS-QOL questionnaire. Central supply and quality control of donor material will be used to control bias.

Primary endpoint is improvement of IBS-SSS (Severity Score System) compared to baseline. Secondary endpoints include changes in IBS-QOL, short term safety and one year follow up to control long term effects, safety and changes in and acceptance of donor microbiome after AMR using16S rDNA sequencing and quantitative diversity analysis.

Description:

This study assesses allogeneic microbiota reconstitution (AMR) as novel treatment to improve symptoms and quality of life of patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

The investigators will perform a prospective multicenter, 2:1 randomized, double-blinded, placebo-controlled trial of AMR in patients with IBS-D diagnosed according to Rome III criteria and the IBS-QOL questionnaire.

The experimental intervention is an infusion of donor feces via gastroscopy. The placebo intervention is an infusion of sterile saline via gastroscopy.

Planned number of patients included in the study: 42 patients Planned per-protocol group: 33 patients

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: May 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• written informed consent

• irritable bowel syndrome of diarrhea-predominant type according to ROME III criteria

• Symptoms for > 1 year before study inclusion

• persisting symptoms > 1 year before study inclusion

• relevant symptoms with reduced Quality of Life (IBS-QOL < 60 Points)

• no specific findings in gastroscopy and colonoscopy with biopsies in the last 2 years

Exclusion Criteria:

• chronic inflammatory diseases

• gastrointestinal infectious diseases

• microscopic colitis

• celiac disease

• diarrhea caused by fructose- or lactose intolerance

• gastrointestinal malignancies or intestinal polyps

• irritable bowel syndrome of other type than IBS-D

• bile acid diarrhea

• constipation

• symptoms caused by other diseases than IBS-D

• dementia

• abdominal surgery in the last months

• antibiotic therapy in the last 3 months

• pregnancy

• linguistic barrier for informed consent

Related Conditions & MeSH terms

• Diarrhea
• Diarrhea-predominant Irritable Bowel Syndrome
• Irritable Bowel Syndrome
• Syndrome

Intervention

Procedure:
• Allogeneic microbiota reconstitution
gastroscopic microbiota Infusion (Verum)
• Placebo-Allogeneic microbiota reconstitution
gastroscopic saline Infusion (placebo)

Locations

Country	Name	City	State
Germany	Helios Klinikum Krefeld	Krefeld
Germany	Ulm University Hospital	Ulm

Sponsors (5)

Lead Sponsor	Collaborator
University of Ulm	Assign International, Berlin, Germany, Charite University, Berlin, Germany, Helios Klinikum Krefeld, Klinikum Ludwigsburg

Country where clinical trial is conducted

Germany, 

References & Publications (22)

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Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15. — View Citation

Ohman L, Simrén M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010 Mar;7(3):163-73. doi: 10.1038/nrgastro.2010.4. Epub 2010 Jan 26. Review. — View Citation

Parkes GC, Rayment NB, Hudspith BN, Petrovska L, Lomer MC, Brostoff J, Whelan K, Sanderson JD. Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome. Neurogastroenterol Motil. 2012 Jan;24(1):31-9. doi: 10.1111/j.1365-2982.2011.01803.x. Epub 2011 Nov 9. — View Citation

Rajilic-Stojanovic M, Heilig HG, Tims S, Zoetendal EG, de Vos WM. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012 Oct 15. doi: 10.1111/1462-2920.12023. [Epub ahead of print] — View Citation

Simrén M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, Verdu EF, Whorwell PJ, Zoetendal EG; Rome Foundation Committee. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013 Jan;62(1):159-76. doi: 10.1136/gutjnl-2012-302167. Epub 2012 Jun 22. — View Citation

Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009 May;136(6):1979-88. doi: 10.1053/j.gastro.2009.02.074. Epub 2009 May 7. Review. — View Citation

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16. — View Citation

Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014 Jan;29(1):52-9. doi: 10.1111/jgh.12322. — View Citation

Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. Erratum in: JAMA. 2015 Feb 17;313(7):729. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decrease of the IBS-SSS questionnaire > 105 Points compared to baseline		90 days after intervention
Secondary	Improvement of IBS-QOL using IBS-QOL-questionnaire compared to baseline		90 days and 1 year after intervention
Secondary	Changes and acceptance of donor microbiome (16S rDNA-analysis)	16S rDNA-analysis for microbiome biodiversity, correlation to IBS-Symptom Severity Score (IBS-SSS)	90 days after intervention
Secondary	Number of participants with treatment related adverse events		follow-up 1 year