The Effect of Fecal Microbiota Transplantation in Ankylosing Spondylitis (AS) Patients. (ASGUT)

Hospital District of Helsinki and Uusimaa

Status and phase

Unknown

Early Phase 1

Conditions

Ankylosing Spondylitis

Treatments

Other: Fecal microbiota transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT03726645

HospitalDHU/Rheumatology

Details and patient eligibility

About

Ankylosing spondylitis (AS) patients often have subclinical gut wall inflammation. Gut dysbiosis has been associated with both AS and Crohn disease, both of which have several features in common. Gut dysbiosis is associated with specific microbial profile in AS patients. Fecal microbiota transplantation (FMT) has been proved to be safe and effective treatment for recurrent Clostridium difficile infection, and the change in gut microbiota is shown to be long lasting. It has led to interest to study its effect on different inflammatory conditions associated with gut dysbiosis.

We hypothesize that dysbiosis in AS leads to inflammasome overactivation on gut mucosa. We aim to study the role of gut inflammation, gut microbiota and inflammasome activation in pathogenesis of AS, and the effect of FMT on these factors, as well as clinical activity, in AS patients.

Full description

This is a double-blind placebo- controlled randomized pilot study with 20 patients with active AS from 2 Finnish outpatient clinics. An ileocolonoscopy will be performed to all patients. 10 patients will receive FMT with feces of one of two healthy donors, and 10 patients with their own feces during ileocolonoscopy. Ileal and colonic biopsies will be taken to assess gut wall inflammation and mucosal microbiota composition. Ileocolonoscopy will be controlled in 6 months in patients with macroscopic inflammatory lesions in the first colonoscopy. From mucosal biopsies we will assess intestinal mucosal structure, inflammasome activity, cytokine expression, and the mucin layer thickness and the amount of bacterial LPS (lipopolysaccharide), which are associated with mucosal integrity. Blood levels of zonulin and LPS as indicators of mucosal permeability and bacterial penetrance will be assessed. Fecal samples will be collected repeatedly to measure fecal calprotectin, and to assess the bacterial profile changes. From mucosal biopsies and fecal samples microbial DNA will be segregated and bacterial species sorted by rRNA- based sequence technique. Clinical activity of AS will be assessed in follow-up visits as well as repeated BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index) and MASES (Maastricht Ankylosing Spondylitis Enthesitis Score) evaluations, and measurement of CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate). Follow-up time is 12 months.

Enrollment

20 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of AS by either the 1984 New York criteria or the ASAS (Assessment of SpondyloArthritis International Society) criteria for axial spondyloarthritis.
Active disease measured by BASDAI > 4.
Availability of consecutive fecal samples over 1 year period.
Compliance to attend ileocolonoscopy and FMT procedure.

Exclusion criteria

Diagnosis of inflammatory bowel disease.
Antibiotic therapy within the last 3 months.
Use of any probiotics within the last 3 months.
Pregnancy.
Unability to provide a written consent.
Other reason which by the opinion of the investigator makes patient ineligible for the study.