Efficacy and Safety of Fecal Microbiota Transplantation in Peripheral Psoriatic Arthritis (FLORA)

December 4, 2020 updated by: Torkell Ellingsen, Odense University Hospital

Efficacy and Safety of Fecal Microbiota Transplantation (FMT) in Patients With Peripheral Psoriatic Arthritis: a 6-month, Double-Blind, Randomized, Placebo-Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Odense, Denmark, 5000
        • Dept. of Rheumatology at Odense University Hospital
      • Silkeborg, Denmark, 8600
        • Diagnostic Centre at Silkeborg Regional Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fecal microbiota transplantation (FMT)
Drug: 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.
Drug: Methotrexate (MTX)
Weekly methotrexate in maximum tolerable dosis
Sham Comparator: Placebo (saline)
Drug: Methotrexate (MTX)
Weekly methotrexate in maximum tolerable dosis
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment failure
Time Frame: 6 months (+/- 14 days)

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:

  • Need for more than 1 intra-articular glucocorticoid injection due to disease activity.
  • Need for change to other conventional DMARDs (at the moment oral leflunomide, sulfasalazin or ciclosporin) according to the updated Danish guideline treatment due to disease activity.
  • Need for biologic treatment according to the updated Danish guideline treatment due to severe disease activity.
6 months (+/- 14 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Short Health Assessment Questionnaire (2-page HAQ)
Time Frame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)

Proportion of patients in each group achieving

  • ACR20 response criteria
  • ACR50 response criteria
  • ACR70 response criteria

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)
Time Frame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
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)
Time Frame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: Baseline, 3 months (+/- 7 days), 6 months (+/- 14 days)
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
Time Frame: 6 months (+/- 14 days)
Number of adverse events in each group.
6 months (+/- 14 days)
Number of Patients with Adverse Events
Time Frame: 6 months (+/- 14 days)
Number of patients with at least one adverse event in each group.
6 months (+/- 14 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Odense University Hospital

Collaborators

University of Southern Denmark
Region of Southern Denmark
Odense Patient Data Explorative Network
The Danish Rheumatism Association
The Psoriasis Association, Denmark
Manufacturer Vilhelm Pedersen Foundation
The Danish Regions (Medicinpuljen)

Investigators

  • Principal Investigator: Torkell J. Ellingsen, Prof PhD, Odense University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2017

Primary Completion (Actual)

June 2, 2020

Study Completion (Actual)

June 2, 2020

Study Registration Dates

First Submitted

February 13, 2017

First Submitted That Met QC Criteria

February 16, 2017

First Posted (Actual)

February 23, 2017

Study Record Updates

Last Update Posted (Actual)

December 7, 2020

Last Update Submitted That Met QC Criteria

December 4, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OUH-DC-FLORA-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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