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

NCT ID: NCT03726645

Last Updated: 2019-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

EARLY_PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-24

Study Completion Date

2020-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ankylosing Spondylitis

Keywords

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ankylosing spondylitis fecal microbiota transplantation intestinal mucosal immunity dysbiosis microbiome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
FMT type (donor/own feces) randomization is done by a study nurse.

Study Groups

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Study group

Allogeneic fecal microbiota transplantation (from donor)

Group Type ACTIVE_COMPARATOR

Fecal microbiota transplantation

Intervention Type OTHER

Fecal microbiota transplantation

Control group

Autologous fecal microbiota transplantation (own stool)

Group Type PLACEBO_COMPARATOR

Fecal microbiota transplantation

Intervention Type OTHER

Fecal microbiota transplantation

Interventions

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Fecal microbiota transplantation

Fecal microbiota transplantation

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital District of Helsinki and Uusimaa

OTHER

Sponsor Role lead

Responsible Party

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Johanna Hiltunen

MD, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kari K Eklund, PhD, MD

Role: STUDY_DIRECTOR

Hospital District of Helsinki and Uusimaa

Locations

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Hospital District of Helsinki and Uusimaa, Department of Rheumatology

Helsinki, Uusimaa, Finland

Site Status

Countries

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Finland

References

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Reference Type DERIVED
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Other Identifiers

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HospitalDHU/Rheumatology

Identifier Type: -

Identifier Source: org_study_id