Efficacy and Safety of Fecal Microbiota Transplantation in Peripheral Psoriatic Arthritis

NCT ID: NCT03058900

Last Updated: 2020-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-16

Study Completion Date

2020-06-02

Brief Summary

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An abnormal intestinal microbiota may be the mediator of the common inflammatory pathways seen in psoriatic arthritis. This study will explore clinical aspects associated with modifying the intestinal microbiota by infusing fecal donor microbiota into the small intestine of psoriatic arthritis patients with a minimum of three swollen joints despite at least three months of methotrexate treatment.

Detailed Description

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Recent years have seen growing recognition of the complexity of the role of the microbiota in shaping the immune system and its potential effects for health and disease. In particular, the gut bacteria composition has been associated with the pathogenesis of autoimmune and inflammatory diseases. Intriguingly, presence of intestinal inflammation in psoriatic arthritis (PsA) patients has been documented in several studies. Also, in genetically predisposed patients reactive arthritis, which share some of the clinical manifestations of PsA, can be triggered by certain types of bacterial gut infections. Furthermore, a recent study has reported that several intestinal bacteria including Akkermansia and Ruminoccocus, which are known to play an important role in maintaining gut homeostasis, were practically absent in PsA patients. Mechanisms through which the microbiota may be involved in the pathogenesis of PsA include an abnormal activation of the gut-associated lymphoid tissue (GALT) and/or an altered mucosal permeability thus compromising the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules.

By conducting a double-blinded, randomized, placebo-controlled trial of a non-related donor fecal microbiota transplantation (FMT) infused into the small intestine, this study will reveal whether FMT is more effective than an identically appearing placebo (saline) in reducing disease activity in psoriatic arthritis patients presenting with a minimum of three swollen joints despite at least three months of methotrexate treatment (maximal tolerable dosis ≥ 15 mg/week). All patients will throughout the study continue their individual treatment with weekly methotrexate.

Conditions

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Psoriatic Arthritis

Keywords

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Fecal Microbiota Transplantation FMT Randomized Controlled Trial Intestinal microbiome RCT Faecal microbiota transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
Double-Blind

Study Groups

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Fecal microbiota transplantation (FMT)

Group Type EXPERIMENTAL

Fecal microbiota transplantation (FMT)

Intervention Type DRUG

One fecal microbiota transplantation is performed at baseline using gastroscopic guidance. The transplant consists of 50 g feces obtained from a healthy non-related donor. The donor feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 250 mL and its temperature will be 37 degrees celsius when infused into the small intestine of the recipient.

Methotrexate (MTX)

Intervention Type DRUG

Weekly methotrexate in maximum tolerable dosis

Placebo (saline)

Group Type SHAM_COMPARATOR

Drug: Placebo (saline)

Intervention Type OTHER

One identical appearing sham procedure is performed at baseline using gastroscopic guidance. 250 mL saline (NaCl 0.9%) is infused into the small intestine of the recipient.

Methotrexate (MTX)

Intervention Type DRUG

Weekly methotrexate in maximum tolerable dosis

Interventions

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Fecal microbiota transplantation (FMT)

One fecal microbiota transplantation is performed at baseline using gastroscopic guidance. The transplant consists of 50 g feces obtained from a healthy non-related donor. The donor feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 250 mL and its temperature will be 37 degrees celsius when infused into the small intestine of the recipient.

Intervention Type DRUG

Drug: Placebo (saline)

One identical appearing sham procedure is performed at baseline using gastroscopic guidance. 250 mL saline (NaCl 0.9%) is infused into the small intestine of the recipient.

Intervention Type OTHER

Methotrexate (MTX)

Weekly methotrexate in maximum tolerable dosis

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of psoriatic arthritis according to the Classification Criteria for Psoriatic Arthritis (CASPAR criteria).
* Presence of active peripheral psoriatic arthritis defined as ≥ 3 swollen joints.
* Methotrexate (≥ 15mg/week (maximal tolerable dosage)) for a minimum of 3 months prior to study inclusion.

Exclusion Criteria

* Other inflammatory rheumatic diseases than PsA.
* Current axial disease activity or severe peripheral joint activity demanding immediate change of treatment or contraindicating placebo treatment for 6 months.
* History of severe MTX toxicity or allergic reactions.
* Current biological treatment and biological treatment within the last 6 months.
* Inflammatory bowel disease, celiac disease, food allergy, or other intestinal diseases.
* Current cancer or severe chronic infections.
* Pregnant or breastfeeding women.
* Systemic and/or local intra-articular or peritendinous steroid injections within 3 months of inclusion.
* Non-MTX DMARD treatment within three months of inclusion.
* Antibiotics within 3 months of inclusion.
* Not wishing to participate or unsuited for project evaluation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Region of Southern Denmark

OTHER

Sponsor Role collaborator

University of Southern Denmark

OTHER

Sponsor Role collaborator

The Danish Rheumatism Association

OTHER

Sponsor Role collaborator

Odense Patient Data Explorative Network

OTHER

Sponsor Role collaborator

The Psoriasis Association, Denmark

UNKNOWN

Sponsor Role collaborator

Manufacturer Vilhelm Pedersen Foundation

OTHER

Sponsor Role collaborator

The Danish Regions (Medicinpuljen)

UNKNOWN

Sponsor Role collaborator

Odense University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Torkell Ellingsen

Clinical professor/Head of research and chief consultant MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Torkell J. Ellingsen, Prof PhD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

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Dept. of Rheumatology at Odense University Hospital

Odense, , Denmark

Site Status

Diagnostic Centre at Silkeborg Regional Hospital

Silkeborg, , Denmark

Site Status

Countries

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Denmark

References

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Coates LC, Conaghan PG, Emery P, Green MJ, Ibrahim G, MacIver H, Helliwell PS. Sensitivity and specificity of the classification of psoriatic arthritis criteria in early psoriatic arthritis. Arthritis Rheum. 2012 Oct;64(10):3150-5. doi: 10.1002/art.34536.

Reference Type BACKGROUND
PMID: 22576997 (View on PubMed)

Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972.

Reference Type BACKGROUND
PMID: 16871531 (View on PubMed)

Kingsley GH, Kowalczyk A, Taylor H, Ibrahim F, Packham JC, McHugh NJ, Mulherin DM, Kitas GD, Chakravarty K, Tom BD, O'Keeffe AG, Maddison PJ, Scott DL. A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford). 2012 Aug;51(8):1368-77. doi: 10.1093/rheumatology/kes001. Epub 2012 Feb 17.

Reference Type BACKGROUND
PMID: 22344575 (View on PubMed)

Statnikov A, Alekseyenko AV, Li Z, Henaff M, Perez-Perez GI, Blaser MJ, Aliferis CF. Microbiomic signatures of psoriasis: feasibility and methodology comparison. Sci Rep. 2013;3:2620. doi: 10.1038/srep02620.

Reference Type BACKGROUND
PMID: 24018484 (View on PubMed)

Eppinga H, Konstantinov SR, Peppelenbosch MP, Thio HB. The microbiome and psoriatic arthritis. Curr Rheumatol Rep. 2014 Mar;16(3):407. doi: 10.1007/s11926-013-0407-2.

Reference Type BACKGROUND
PMID: 24474190 (View on PubMed)

Jacques P, Elewaut D. Joint expedition: linking gut inflammation to arthritis. Mucosal Immunol. 2008 Sep;1(5):364-71. doi: 10.1038/mi.2008.24. Epub 2008 Jul 9.

Reference Type BACKGROUND
PMID: 19079200 (View on PubMed)

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013 Nov 5;2:e01202. doi: 10.7554/eLife.01202.

Reference Type BACKGROUND
PMID: 24192039 (View on PubMed)

Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol. 2014 Jan;26(1):101-7. doi: 10.1097/BOR.0000000000000008.

Reference Type BACKGROUND
PMID: 24247114 (View on PubMed)

Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015 Jan;67(1):128-39. doi: 10.1002/art.38892.

Reference Type BACKGROUND
PMID: 25319745 (View on PubMed)

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015 Aug;21(8):895-905. doi: 10.1038/nm.3914. Epub 2015 Jul 27.

Reference Type BACKGROUND
PMID: 26214836 (View on PubMed)

Yeoh N, Burton JP, Suppiah P, Reid G, Stebbings S. The role of the microbiome in rheumatic diseases. Curr Rheumatol Rep. 2013 Mar;15(3):314. doi: 10.1007/s11926-012-0314-y.

Reference Type BACKGROUND
PMID: 23378145 (View on PubMed)

Scarpa R, Manguso F, D'Arienzo A, D'Armiento FP, Astarita C, Mazzacca G, Ayala F. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol. 2000 May;27(5):1241-6.

Reference Type BACKGROUND
PMID: 10813294 (View on PubMed)

Van Praet L, Van den Bosch F, Mielants H, Elewaut D. Mucosal inflammation in spondylarthritides: past, present, and future. Curr Rheumatol Rep. 2011 Oct;13(5):409-15. doi: 10.1007/s11926-011-0198-2.

Reference Type BACKGROUND
PMID: 21744132 (View on PubMed)

Lindqvist U, Kristjansson G, Pihl-Lundin I, Hagforsen E, Michaelsson G. Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris. J Rheumatol. 2006 May;33(5):924-7. Epub 2006 Mar 15.

Reference Type BACKGROUND
PMID: 16541478 (View on PubMed)

Morgan XC, Huttenhower C. Meta'omic analytic techniques for studying the intestinal microbiome. Gastroenterology. 2014 May;146(6):1437-1448.e1. doi: 10.1053/j.gastro.2014.01.049. Epub 2014 Jan 28.

Reference Type BACKGROUND
PMID: 24486053 (View on PubMed)

Klingberg E, Carlsten H, Hilme E, Hedberg M, Forsblad-d'Elia H. Calprotectin in ankylosing spondylitis--frequently elevated in feces, but normal in serum. Scand J Gastroenterol. 2012 Apr;47(4):435-44. doi: 10.3109/00365521.2011.648953. Epub 2012 Jan 10.

Reference Type BACKGROUND
PMID: 22229862 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23323867 (View on PubMed)

Smith MB, Kelly C, Alm EJ. Policy: How to regulate faecal transplants. Nature. 2014 Feb 20;506(7488):290-1. doi: 10.1038/506290a. No abstract available.

Reference Type BACKGROUND
PMID: 24558658 (View on PubMed)

Toupin-April K, Barton J, Fraenkel L, Li L, Grandpierre V, Guillemin F, Rader T, Stacey D, Legare F, Jull J, Petkovic J, Scholte-Voshaar M, Welch V, Lyddiatt A, Hofstetter C, De Wit M, March L, Meade T, Christensen R, Gaujoux-Viala C, Suarez-Almazor ME, Boonen A, Pohl C, Martin R, Tugwell PS. Development of a Draft Core Set of Domains for Measuring Shared Decision Making in Osteoarthritis: An OMERACT Working Group on Shared Decision Making. J Rheumatol. 2015 Dec;42(12):2442-7. doi: 10.3899/jrheum.141205. Epub 2015 Apr 15.

Reference Type BACKGROUND
PMID: 25877502 (View on PubMed)

Bruce B, Fries JF. The Health Assessment Questionnaire (HAQ). Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S14-8.

Reference Type BACKGROUND
PMID: 16273780 (View on PubMed)

Faria JR, Aarao AR, Jimenez LM, Silva OH, Avelleira JC. Inter-rater concordance study of the PASI (Psoriasis Area and Severity Index). An Bras Dermatol. 2010 Sep-Oct;85(5):625-9. doi: 10.1590/s0365-05962010000500005.

Reference Type BACKGROUND
PMID: 21152786 (View on PubMed)

Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, Sampalis J, Conner-Spady B. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009 Jun;68(6):948-53. doi: 10.1136/ard.2007.084244. Epub 2008 Jun 4.

Reference Type BACKGROUND
PMID: 18524792 (View on PubMed)

Kragsnaes MS, Jensen JRB, Nilsson AC, Malik MI, Munk HL, Pedersen JK, Horn HC, Kruhoffer M, Kristiansen K, Mullish BH, Marchesi JR, Kjeldsen J, Rottger R, Ellingsen T. Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial. RMD Open. 2024 Jan 30;10(1):e003750. doi: 10.1136/rmdopen-2023-003750.

Reference Type DERIVED
PMID: 38296309 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36058784 (View on PubMed)

Kragsnaes MS, Sodergren ST, Kjeldsen J, Horn HC, Munk HL, Pedersen JK, Klinkby CS, de Wit M, Ahlmark NG, Tjornhoj-Thomsen T, Ellingsen T. Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study. BMJ Open. 2021 Mar 8;11(3):e039471. doi: 10.1136/bmjopen-2020-039471.

Reference Type DERIVED
PMID: 34006020 (View on PubMed)

Kragsnaes MS, Kjeldsen J, Horn HC, Munk HL, Pedersen JK, Just SA, Ahlquist P, Pedersen FM, de Wit M, Moller S, Andersen V, Kristiansen K, Kinggaard Holm D, Holt HM, Christensen R, Ellingsen T. Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial. Ann Rheum Dis. 2021 Sep;80(9):1158-1167. doi: 10.1136/annrheumdis-2020-219511. Epub 2021 Apr 29.

Reference Type DERIVED
PMID: 33926922 (View on PubMed)

Kragsnaes MS, Kjeldsen J, Horn HC, Munk HL, Pedersen FM, Holt HM, Pedersen JK, Holm DK, Glerup H, Andersen V, Fredberg U, Kristiansen K, Christensen R, Ellingsen T. Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial. BMJ Open. 2018 Apr 27;8(4):e019231. doi: 10.1136/bmjopen-2017-019231.

Reference Type DERIVED
PMID: 29703851 (View on PubMed)

Other Identifiers

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OUH-DC-FLORA-01

Identifier Type: -

Identifier Source: org_study_id