The Effect of Fecal Microbiota Transplantation in Ankylosing Spondylitis (AS) Patients.

NCT03726645 | Unknown Early Phase 1

• 1 other identifier: HospitalDHU/Rheumatology
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Ankylosing spondylitis (AS) patients often have subclinical gut wall inflammation. Gut dysbiosis has been associated with both AS and Crohn disease, both of which have several features in common. Gut dysbiosis is associated with specific microbial profile in AS patients. Fecal microbiota transplantation (FMT) has been proved to be safe and effective treatment for recurrent Clostridium difficile infection, and the change in gut microbiota is shown to be long lasting. It has led to interest to study its effect on different inflammatory conditions associated with gut dysbiosis. We hypothesize that dysbiosis in AS leads to inflammasome overactivation on gut mucosa. We aim to study the role of gut inflammation, gut microbiota and inflammasome activation in pathogenesis of AS, and the effect of FMT on these factors, as well as clinical activity, in AS patients.

Conditions

Ankylosing Spondylitis

Keywords

ankylosing spondylitis; fecal microbiota transplantation; intestinal mucosal immunity; dysbiosis; microbiome

Outcome Measures

Primary Outcomes (1)

• The effect of FMT (fecal microbiota transplantation) on the clinical activity of ankylosing spondylitis (AS) as assessed by change in BASDAI (Bath Ankylosing Spondylitis Disease Activity Index).

  BASDAI scale 0-10 (the higher the score the more severe the symptoms). Decrease in BASDAI indicates positive outcome.

  5 measurements within 12 months

Secondary Outcomes (17)

• The effect of FMT on the clinical activity of AS as assessed by change in BASFI (Bath Ankylosing Spondylitis Functional Index).

  5 measurements within 12 months.

• The effect of FMT on the clinical activity of AS as assessed by change in MASES (Maastricht Ankylosing Spondylitis Enthesitis Score).

  5 measurements within 12 months.

• The effect of FMT on C-reactive protein (CRP) concentration.

  7 measurements within 12 months.

• The effect of FMT on erythrocyte sedimentation rate (ESR) level.

  7 measurements within 12 months.

• The effect of FMT on gut wall inflammation as assessed by change in fecal calprotectin (F-calpro) level.

  7 measurements within 12 months.

Study Arms (2)

Study group

ACTIVE COMPARATOR

Allogeneic fecal microbiota transplantation (from donor)

Other: Fecal microbiota transplantation

Control group

PLACEBO COMPARATOR

Autologous fecal microbiota transplantation (own stool)

Other: Fecal microbiota transplantation

Interventions

Fecal microbiota transplantation OTHER

Fecal microbiota transplantation

Control group; Study group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AS by either the 1984 New York criteria or the ASAS (Assessment of SpondyloArthritis International Society) criteria for axial spondyloarthritis.
• Active disease measured by BASDAI \> 4.
• Availability of consecutive fecal samples over 1 year period.
• Compliance to attend ileocolonoscopy and FMT procedure.

You may not qualify if:

• Diagnosis of inflammatory bowel disease.
• Antibiotic therapy within the last 3 months.
• Use of any probiotics within the last 3 months.
• Pregnancy.
• Unability to provide a written consent.
• Other reason which by the opinion of the investigator makes patient ineligible for the study.

Sponsors & Collaborators

• Hospital District of Helsinki and Uusimaa: lead

Study Sites (1)

Hospital District of Helsinki and Uusimaa, Department of Rheumatology

Helsinki, Uusimaa, 00029, Finland

Location

Related Publications (21)

• Anderson JL, Edney RJ, Whelan K. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther. 2012 Sep;36(6):503-16. doi: 10.1111/j.1365-2036.2012.05220.x. Epub 2012 Jul 25.

  PMID: 22827693 BACKGROUND

• Breban M, Tap J, Leboime A, Said-Nahal R, Langella P, Chiocchia G, Furet JP, Sokol H. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis. 2017 Sep;76(9):1614-1622. doi: 10.1136/annrheumdis-2016-211064. Epub 2017 Jun 12.

  PMID: 28606969 BACKGROUND

• Ciccia F, Bombardieri M, Principato A, Giardina A, Tripodo C, Porcasi R, Peralta S, Franco V, Giardina E, Craxi A, Pitzalis C, Triolo G. Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2009 Apr;60(4):955-65. doi: 10.1002/art.24389.

  PMID: 19333939 BACKGROUND

• Ciccia F, Ferrante A, Triolo G. Intestinal dysbiosis and innate immune responses in axial spondyloarthritis. Curr Opin Rheumatol. 2016 Jul;28(4):352-8. doi: 10.1097/BOR.0000000000000296.

  PMID: 27214393 BACKGROUND

• Ciccia F, Guggino G, Rizzo A, Alessandro R, Luchetti MM, Milling S, Saieva L, Cypers H, Stampone T, Di Benedetto P, Gabrielli A, Fasano A, Elewaut D, Triolo G. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017 Jun;76(6):1123-1132. doi: 10.1136/annrheumdis-2016-210000. Epub 2017 Jan 9.

  PMID: 28069576 BACKGROUND

• Costello ME, Ciccia F, Willner D, Warrington N, Robinson PC, Gardiner B, Marshall M, Kenna TJ, Triolo G, Brown MA. Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis. Arthritis Rheumatol. 2015 Mar;67(3):686-691. doi: 10.1002/art.38967.

  PMID: 25417597 BACKGROUND

• De Vos M, Mielants H, Cuvelier C, Elewaut A, Veys E. Long-term evolution of gut inflammation in patients with spondyloarthropathy. Gastroenterology. 1996 Jun;110(6):1696-703. doi: 10.1053/gast.1996.v110.pm8964393.

  PMID: 8964393 BACKGROUND

• Huttenhower C, Kostic AD, Xavier RJ. Inflammatory bowel disease as a model for translating the microbiome. Immunity. 2014 Jun 19;40(6):843-54. doi: 10.1016/j.immuni.2014.05.013.

  PMID: 24950204 BACKGROUND

• Jalanka J, Mattila E, Jouhten H, Hartman J, de Vos WM, Arkkila P, Satokari R. Long-term effects on luminal and mucosal microbiota and commonly acquired taxa in faecal microbiota transplantation for recurrent Clostridium difficile infection. BMC Med. 2016 Oct 11;14(1):155. doi: 10.1186/s12916-016-0698-z.

  PMID: 27724956 BACKGROUND

• Knodler LA, Crowley SM, Sham HP, Yang H, Wrande M, Ma C, Ernst RK, Steele-Mortimer O, Celli J, Vallance BA. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe. 2014 Aug 13;16(2):249-256. doi: 10.1016/j.chom.2014.07.002.

  PMID: 25121752 BACKGROUND

• Leirisalo-Repo M, Turunen U, Stenman S, Helenius P, Seppala K. High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum. 1994 Jan;37(1):23-31. doi: 10.1002/art.1780370105.

  PMID: 8129761 BACKGROUND

• Mattila E, Uusitalo-Seppala R, Wuorela M, Lehtola L, Nurmi H, Ristikankare M, Moilanen V, Salminen K, Seppala M, Mattila PS, Anttila VJ, Arkkila P. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012 Mar;142(3):490-6. doi: 10.1053/j.gastro.2011.11.037. Epub 2011 Dec 7.

  PMID: 22155369 BACKGROUND

• Nurmi K, Virkanen J, Rajamaki K, Niemi K, Kovanen PT, Eklund KK. Ethanol inhibits activation of NLRP3 and AIM2 inflammasomes in human macrophages--a novel anti-inflammatory action of alcohol. PLoS One. 2013 Nov 11;8(11):e78537. doi: 10.1371/journal.pone.0078537. eCollection 2013.

  PMID: 24244322 BACKGROUND

• Nurmi K, Kareinen I, Virkanen J, Rajamaki K, Kouri VP, Vaali K, Levonen AL, Fyhrquist N, Matikainen S, Kovanen PT, Eklund KK. Hemin and Cobalt Protoporphyrin Inhibit NLRP3 Inflammasome Activation by Enhancing Autophagy: A Novel Mechanism of Inflammasome Regulation. J Innate Immun. 2017;9(1):65-82. doi: 10.1159/000448894. Epub 2016 Sep 22.

  PMID: 27655219 BACKGROUND

• Rajamaki K, Lappalainen J, Oorni K, Valimaki E, Matikainen S, Kovanen PT, Eklund KK. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One. 2010 Jul 23;5(7):e11765. doi: 10.1371/journal.pone.0011765.

  PMID: 20668705 BACKGROUND

• Rajamaki K, Nordstrom T, Nurmi K, Akerman KE, Kovanen PT, Oorni K, Eklund KK. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem. 2013 May 10;288(19):13410-9. doi: 10.1074/jbc.M112.426254. Epub 2013 Mar 25.

  PMID: 23530046 BACKGROUND

• Tailford LE, Crost EH, Kavanaugh D, Juge N. Mucin glycan foraging in the human gut microbiome. Front Genet. 2015 Mar 19;6:81. doi: 10.3389/fgene.2015.00081. eCollection 2015.

  PMID: 25852737 BACKGROUND

• Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E, Hammer RE. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994 Dec 1;180(6):2359-64. doi: 10.1084/jem.180.6.2359.

  PMID: 7964509 BACKGROUND

• Tito RY, Cypers H, Joossens M, Varkas G, Van Praet L, Glorieus E, Van den Bosch F, De Vos M, Raes J, Elewaut D. Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis. Arthritis Rheumatol. 2017 Jan;69(1):114-121. doi: 10.1002/art.39802. Epub 2016 Dec 1.

  PMID: 27390077 BACKGROUND

• Van Praet L, Van den Bosch FE, Jacques P, Carron P, Jans L, Colman R, Glorieus E, Peeters H, Mielants H, De Vos M, Cuvelier C, Elewaut D. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis. 2013 Mar;72(3):414-7. doi: 10.1136/annrheumdis-2012-202135. Epub 2012 Nov 8.

  PMID: 23139267 BACKGROUND

• Parthasarathy R, Santiago F, McCluskey P, Kaakoush NO, Tedla N, Wakefield D. The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies. Trends Microbiol. 2023 Feb;31(2):142-158. doi: 10.1016/j.tim.2022.08.008. Epub 2022 Sep 1.

  PMID: 36058784 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing; Dysbiosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Kari K Eklund, PhD, MD

  Hospital District of Helsinki and Uusimaa

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: FMT type (donor/own feces) randomization is done by a study nurse.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: October 31, 2018
• Study Start: October 24, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: May 31, 2019

Record last verified: 2019-05

Locations

FI (1)