Title
Efficacy and Safety of Fecal Microbiota Transplantation in Peripheral Psoriatic Arthritis
Efficacy and Safety of Fecal Microbiota Transplantation (FMT) in Patients With Peripheral Psoriatic Arthritis: a 6-month, Double-Blind, Randomized, Placebo-Controlled Trial
Phase
N/ALead Sponsor
University of Southern DenmarkStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Psoriatic ArthritisIntervention/Treatment
Fecal microbiota transplantation (FMT) Drug: Placebo (saline) Methotrexate (MTX)Study Participants
31An 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.
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.
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.
Weekly methotrexate in maximum tolerable dosis
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.
