Efficacy and Safety of Fecal Microbiota Transplantation in Peripheral Psoriatic Arthritis (FLORA)
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| ClinicalTrials.gov Identifier: NCT03058900 |
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Recruitment Status :
Recruiting
First Posted : February 23, 2017
Last Update Posted : January 4, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriatic Arthritis | Drug: Fecal microbiota transplantation (FMT) Other: Drug: Placebo (saline) Drug: Methotrexate (MTX) | Not Applicable |
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 (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Outcomes Assessor) |
| Masking Description: | Double-Blind |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 16, 2017 |
| Estimated Primary Completion Date : | July 1, 2020 |
| Estimated Study Completion Date : | July 1, 2020 |
| 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) |
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. Drug: Methotrexate (MTX) Weekly methotrexate in maximum tolerable dosis |
- 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.
- 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).
- 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).
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- Number of Adverse Events [ Time Frame: 6 months (+/- 14 days) ]Number of adverse events in each group.
- Number of Patients with Adverse Events [ Time Frame: 6 months (+/- 14 days) ]Number of patients with at least one adverse event in each group.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03058900
| Contact: Torkell J. Ellingsen, Prof PhD | +45 22397306 | torkell.ellingsen@rsyd.dk | |
| Contact: Maja S. Kragsnaes, MD | +45 22982528 | maja.kragsnaes@dadlnet.dk |
| Denmark | |
| Dept. of Rheumatology at Odense University Hospital | Recruiting |
| Odense, Denmark, 5000 | |
| Contact: Torkell J. Ellingsen, Prof PhD torkell.ellingsen@rsyd.dk | |
| Contact: Maja S. Kragsnaes, MD maja.kragsnaes@dadlnet.dk | |
| Sub-Investigator: Maja S. Kragsnaes, MD | |
| Principal Investigator: Torkell J. Ellingsen, Prof PhD | |
| Diagnostic Centre at Silkeborg Regional Hospital | Not yet recruiting |
| Silkeborg, Denmark, 8600 | |
| Contact: Maja S. Kragsnaes, PhD student | |
| Principal Investigator: | Torkell J. Ellingsen, Prof PhD | Odense University Hospital |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Torkell Ellingsen, Clinical professor/Head of research and chief consultant MD PhD, Odense University Hospital |
| ClinicalTrials.gov Identifier: | NCT03058900 History of Changes |
| Other Study ID Numbers: |
OUH-DC-FLORA-01 |
| First Posted: | February 23, 2017 Key Record Dates |
| Last Update Posted: | January 4, 2019 |
| Last Verified: | January 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Fecal Microbiota Transplantation FMT Randomized Controlled Trial |
Intestinal microbiome RCT Faecal microbiota transplantation |
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Arthritis Arthritis, Psoriatic Joint Diseases Musculoskeletal Diseases Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases Bone Diseases Psoriasis Skin Diseases, Papulosquamous Skin Diseases Methotrexate Abortifacient Agents, Nonsteroidal |
Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors |