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| Name | Class |
|---|---|
| Region of Southern Denmark | OTHER |
| University of Southern Denmark | OTHER |
| The Danish Rheumatism Association | OTHER |
| Odense Patient Data Explorative Network |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fecal microbiota transplantation (FMT) | Experimental |
| |
| Placebo (saline) | Sham Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal microbiota transplantation (FMT) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment failure | Proportion of patients in each group who experience treatment failure according to shared decision making between patient and rheumatologist defined as at least one of the following:
| 6 months (+/- 14 days) |
| Measure | Description | Time Frame |
|---|---|---|
| The Short Health Assessment Questionnaire (2-page HAQ) | Change from baseline in the Short Health Assessment Questionnaire (2-page HAQ). | Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| The Dermatology Life Quality Index (DLQI) Questionnaire |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Torkell J. Ellingsen, Prof PhD | Odense University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dept. of Rheumatology at Odense University Hospital | Odense | 5000 | Denmark | |||
| Diagnostic Centre at Silkeborg Regional Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22576997 | Background | 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. | |
| 16871531 | Background | 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. |
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| ID | Term |
|---|---|
| D015535 | Arthritis, Psoriatic |
| ID | Term |
|---|---|
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| D012965 | Sodium Chloride |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
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| OTHER |
| The Psoriasis Association, Denmark | UNKNOWN |
| Manufacturer Vilhelm Pedersen Foundation | OTHER |
| The Danish Regions (Medicinpuljen) | UNKNOWN |
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Double-Blind
|
| Drug: Placebo (saline) | 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) | Drug | Weekly methotrexate in maximum tolerable dosis |
|
Change from baseline in the Dermatology Life Quality Index (DLQI). |
| Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| Patient Reported Gastrointestinal Side Effects | Change from baseline in gastrointestinal symptoms. | Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| Patient Reported Other Side Effects | Change from baseline in other (non-gastrointestinal) symptoms. | Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| The American College of Rheumatology (ACR) Response Criteria | Proportion of patients in each group achieving
A patient will be considered as improved according to the ACR20/50/70 response criteria if she/he has at least 20/50/70% improvement in the two following measures: Tender joint count (68) and swollen joint count (66), and at least 3 of the following 5 measures: Patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ) score, acute phase reactant (CRP). | Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| The Psoriatic Arthritis Response Criteria (PsARC) | Proportion of patients in each group achieving PsARC response criteria. A patient will be considered as improved according to the PsARC response criteria if she/he has an improvement in either joint swelling or tenderness, and in any of 4 other measures: Patient global assessment of articular disease; physician global assessment of articular disease; joint pain or tenderness; joint swelling. | Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| The Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index | Change from baseline in SPARCC Enthesitis Index in the subset of patients who have enthesitis at baseline. | Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| The Psoriasis Area Severity Index (PASI) | Change from baseline in the Psoriasis Area Severity Index (PASI) in the subset of patients who have psoriasis at baseline. | Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| Dactylitis | Change from baseline in the number of digits affected with dactylitis in the subset of patients who have dactylitis at baseline. | Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days) |
| Number of Adverse Events | Number of adverse events in each group. | 6 months (+/- 14 days) |
| Number of Patients with Adverse Events | Number of patients with at least one adverse event in each group. | 6 months (+/- 14 days) |
| Silkeborg |
| 8600 |
| Denmark |
| 22344575 | Background | 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. |
| 24018484 | Background | 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. |
| 24474190 | Background | 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. |
| 19079200 | Background | 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. |
| 24192039 | Background | 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. |
| 24247114 | Background | 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. |
| 25319745 | Background | 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. |
| 26214836 | Background | 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. |
| 23378145 | Background | 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. |
| 10813294 | Background | 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. |
| 21744132 | Background | 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. |
| 16541478 | Background | 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. |
| 24486053 | Background | 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. |
| 22229862 | Background | 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. |
| 23323867 | Background | 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. |
| 24558658 | Background | 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. |
| 25877502 | Background | 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. |
| 16273780 | Background | Bruce B, Fries JF. The Health Assessment Questionnaire (HAQ). Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S14-8. |
| 21152786 | Background | 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. |
| 18524792 | Background | 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. |
| 38296309 | Derived | 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. |
| 36058784 | Derived | 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. |
| 34006020 | Derived | 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. |
| 33926922 | Derived | 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. |
| 29703851 | Derived | 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. |
| D001847 |
| Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D011565 | Psoriasis |
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017606 |
| Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |