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

May 30, 2019 updated by: Johanna Hiltunen, Hospital District of Helsinki and Uusimaa

The Role of Gut Microbiota in the Pathogenesis of Ankylosing Spondylitis (AS), and the Effect of Fecal Microbiota Transplantation on Gut Microbiota, Gut Wall Inflammation and Clinical Activity of AS

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Early Phase 1

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

  • Finland
    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00029
        • Hospital District of Helsinki and Uusimaa, Department of Rheumatology

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 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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
Active Comparator: Study group
Allogeneic fecal microbiota transplantation (from donor)
Other: Fecal microbiota transplantation
Fecal microbiota transplantation
Placebo Comparator: Control group
Autologous fecal microbiota transplantation (own stool)
Other: Fecal microbiota transplantation
Fecal microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effect of FMT (fecal microbiota transplantation) on the clinical activity of ankylosing spondylitis (AS) as assessed by change in BASDAI (Bath Ankylosing Spondylitis Disease Activity Index).
Time Frame: 5 measurements within 12 months
BASDAI scale 0-10 (the higher the score the more severe the symptoms). Decrease in BASDAI indicates positive outcome.
5 measurements within 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effect of FMT on the clinical activity of AS as assessed by change in BASFI (Bath Ankylosing Spondylitis Functional Index).
Time Frame: 5 measurements within 12 months.
BASFI scale 0-10 (the higher the score the more severe the symptoms). Decrease in BASFI indicates positive outcome.
5 measurements within 12 months.
The effect of FMT on the clinical activity of AS as assessed by change in MASES (Maastricht Ankylosing Spondylitis Enthesitis Score).
Time Frame: 5 measurements within 12 months.
MASES scale 0-13 (the higher the score the more severe the symptoms). Decrease in MASES indicates positive outcome.
5 measurements within 12 months.
The effect of FMT on C-reactive protein (CRP) concentration.
Time Frame: 7 measurements within 12 months.
Change in inflammatory parameter CRP concentration indicates positive outcome.
7 measurements within 12 months.
The effect of FMT on erythrocyte sedimentation rate (ESR) level.
Time Frame: 7 measurements within 12 months.
Change in inflammatory parameter ESR level indicates positive outcome.
7 measurements within 12 months.
The effect of FMT on gut wall inflammation as assessed by change in fecal calprotectin (F-calpro) level.
Time Frame: 7 measurements within 12 months.
Change in fecal calprotectin level indicates positive outcome.
7 measurements within 12 months.
The effect of FMT on gut microbiota composition in AS patients.
Time Frame: 7 stool microbial analysis within 12 months.
Change in gut microbiota composition evaluated by stool microbial analysis indicates positive outcome.
7 stool microbial analysis within 12 months.
Association between specific intestinal pathogens and disease activity as assessed by BASDAI score.
Time Frame: 7 stool microbial samples and 5 BASDAI measurements within 12 months.
BASDAI scale 0-10 (the higher the score the more severe the symptoms). Association between specific microbial profile and higher or lower disease activity assessed by BASDAI indicates a positive outcome.
7 stool microbial samples and 5 BASDAI measurements within 12 months.
Association between specific intestinal pathogens and disease activity as assessed by CRP concentration.
Time Frame: 7 stool microbial samples and 7 CRP measurements within 12 months.
Association between specific intestinal pathogens and (higher or lower) CRP concentration compared to patients with different microbial profile indicates a positive outcome.
7 stool microbial samples and 7 CRP measurements within 12 months.
Association between gut wall cytokine expression and disease activity as assessed by BASDAI score.
Time Frame: Intestinal biopsies at baseline.
BASDAI scale 0-10 (the higher the score the more severe the symptoms). Association between the level of cytokine expression and BASDAI score indicates a positive outcome.
Intestinal biopsies at baseline.
Association between gut wall inflammasome activity and disease activity as assessed by BASDAI score.
Time Frame: Intestinal biopsies at baseline.
BASDAI scale 0-10 (the higher the score the more severe the symptoms). Association between gut wall inflammation as assessed by inflammasome activity and disease activity as assessed by BASDAI score indicates a positive outcome.
Intestinal biopsies at baseline.
Association between gut wall cytokine expression and disease activity as assessed by CRP concentration.
Time Frame: Intestinal biopsies at baseline.
Association between gut wall inflammation as assessed by the level of cytokine expression and the disease activity as assessed by CRP concentration indicates a positive outcome.
Intestinal biopsies at baseline.
Association between gut wall inflammasome activity and disease activity as assessed by CRP concentration.
Time Frame: Intestinal biopsies at baseline.
Association between gut wall inflammation as assessed by inflammasome activity and disease activity as assessed by CRP concentration indicates a positive outcome.
Intestinal biopsies at baseline.
Association between F-Calpro level and disease activity as assessed by BASDAI score.
Time Frame: 7 F-Calpro- measurements and 5 BASDAI measurements within 12 months.
Calprotectin- level < 100 ug/l is considered as normal. BASDAI scale 0-10 (the higher the score the more severe the symptoms). Association between gut wall inflammation as assessed by F-Calpro level and disease activity as assessed by BASDAI score indicates a positive outcome.
7 F-Calpro- measurements and 5 BASDAI measurements within 12 months.
Association between F-Calpro level and disease activity as assessed by CRP concentration.
Time Frame: 7 F-Calpro and CRP measurements within 12 months.
Calprotectin- level < 100 ug/l is considered as normal. Association between gut wall inflammation as assessed by F-Calpro and disease activity as assessed by CRP concentration indicates a positive outcome.
7 F-Calpro and CRP measurements within 12 months.
The effect of FMT on gut wall permeability as assessed by blood zonulin concentration.
Time Frame: 5 measurements within 12 months.
Change in zonulin concentration indicates a positive outcome.
5 measurements within 12 months.
The effect of FMT on gut wall bacterial penetrance as assessed by lipopolysaccharide (LPS) concentration.
Time Frame: 5 measurements within 12 months.
Change in LPS concentration indicates a positive outcome.
5 measurements within 12 months.
The effect of FMT on gastrointestinal symptoms as assessed by GSRS (The Gastrointestinal Symptom Rating Scale).
Time Frame: 5 GSRS evaluations within 12 months.
GSRS score scale 15-105. The higher the score the more severe the symptoms. Decrease in GSRS indicates a positive outcome.
5 GSRS evaluations within 12 months.

Collaborators and Investigators

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

Sponsor

Hospital District of Helsinki and Uusimaa

Investigators

  • Study Director: Kari K Eklund, PhD, MD, Hospital District of Helsinki and Uusimaa

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)

October 24, 2018

Primary Completion (Anticipated)

April 1, 2020

Study Completion (Anticipated)

April 1, 2020

Study Registration Dates

First Submitted

March 23, 2018

First Submitted That Met QC Criteria

October 30, 2018

First Posted (Actual)

October 31, 2018

Study Record Updates

Last Update Posted (Actual)

May 31, 2019

Last Update Submitted That Met QC Criteria

May 30, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HospitalDHU/Rheumatology

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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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