Clinical trial NCT03058900: Efficacy and Safety of Fecal Microbiota Transplantation in Peripheral Psoriatic Arthritis
Official title: Efficacy and Safety of Fecal Microbiota Transplantation (FMT) in Patients With Peripheral Psoriatic Arthritis: a 6-month, Double-Blind, Randomized, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Psoriatic Arthritis
Keywords: Fecal Microbiota Transplantation
FMT
Randomized Controlled Trial
Intestinal microbiome
RCT
Faecal microbiota transplantation
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Region of Southern Denmark
name: University of Southern Denmark
name: The Danish Rheumatism Association
name: Odense Patient Data Explorative Network
name: The Psoriasis Association, Denmark
name: Manufacturer Vilhelm Pedersen Foundation
name: The Danish Regions (Medicinpuljen)
First posted: 2017-02-23
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment failure
timeFrame: 6 months (+/- 14 days)
Secondary outcomes:
measure: The Short Health Assessment Questionnaire (2-page HAQ)
timeFrame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: The Dermatology Life Quality Index (DLQI) Questionnaire
timeFrame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: Patient Reported Gastrointestinal Side Effects
timeFrame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: Patient Reported Other Side Effects
timeFrame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: The American College of Rheumatology (ACR) Response Criteria
timeFrame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: The Psoriatic Arthritis Response Criteria (PsARC)
timeFrame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: The Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index
timeFrame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: The Psoriasis Area Severity Index (PASI)
timeFrame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: Dactylitis
timeFrame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
measure: Number of Adverse Events
timeFrame: 6 months (+/- 14 days)
measure: Number of Patients with Adverse Events
timeFrame: 6 months (+/- 14 days)
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Dept. of Rheumatology at Odense University Hospital
city: Silkeborg
country: Denmark
facility: Diagnostic Centre at Silkeborg Regional Hospital
Study officials:
affiliation: Odense University Hospital
name: Torkell J. Ellingsen, Prof PhD
role: PRINCIPAL_INVESTIGATOR
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