Fecal Microbiota Transplantation in Axial Spondyloarthritis

NCT06451588 | Recruiting Phase 2

• 1 other identifier: 537025
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

Although biologic therapy have revolutionized the treatment of Spondyloarthrtitis (SpA), many patients do not experience complete relief of SpA related complaints. It has been established that patients with SpA have an altered composition of microorganisms (microbiota) in the gut compared to healthy controls, and that this correlates to disease activity and respons to therapy. The goal of this randomized double-blind study is to evaluate the efficacy of fecal microbiota transplantation (FMT) in patients with axial SpA with a suboptimal effect of biologic therapy. The main questions it aims to answer are:

• Can FMT reduce disease activity in axial SpA?
• Can FMT alleviate pain and reduce fatigue in axial SpA?
• Is the composition of microorganisms restored to normal in patients with SpA after a treatment with FMT? Participants will receive a single treatment in the form of an enema with either donor FMT or placebo at baseline. The primary endpoint will be evaluated after 90 days, but efficacy and safety will be monitored from baseline until 365 days.

Conditions

Axial Spondyloarthritis; Ankylosing Spondylitis; Dysbiosis; Spondyloarthritis; Spondylitis; Arthritis; Musculoskeletal Diseases; Spinal Disease; Joint Diseases

Keywords

Axial Spondyloarthritis; Microbiome; Fecal Microbiota Transplantation; Microbiota; FMT; RCT

Outcome Measures

Primary Outcomes (1)

• Minimal Clinically Important Improvement

  Proportion of patients that meet the criteria of Minimal Clinically Important Improvement in the donor FMT (dFMT) versus the autologous FMT (aFMT) group at day 90 after treatment. Minimal Clinically Important Improvement is defined by a decrease of ≥1,1 in ASDAS-CRP

  90 days

Secondary Outcomes (18)

• Adverse events

  Day 0-90 and day 91-365

• Ankylosing Spondylitis Disease Activity Score (ASDAS)20

  baseline, day 30, day 60 and day 90

• Bath Ankylosing Spondylitis Disease Activity Index

  baseline, day 30, day 60 and day 90

• Bath Anykylosing Spondylitis Funtional Index

  baseline, day 30, day 60 and day 90

• Patient global assessment

  baseline, day 30, day 60 and day 90

Other Outcomes (2)

• Exploratory endpoint

  baseline and day 90

• Exploratory endpoint

  baseline

Study Arms (4)

Donor A FMT

EXPERIMENTAL

Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.

Drug: FMT

Donor B FMT

EXPERIMENTAL

Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.

Drug: FMT

Donor C FMT

EXPERIMENTAL

Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.

Drug: FMT

Placebo/autologous FMT

PLACEBO COMPARATOR

Placebo treatment will be processed identically to active treatment, but with paritcipants own stool. The patients in the placebo group will consequently receive an enema with 60g of their own feces combined with glycerol and saline as a single treatment at baseline.

Drug: Placebo

Interventions

FMT DRUG

Active FMT

Donor A FMT; Donor B FMT; Donor C FMT

Placebo DRUG

The placebo treatment will be prepared based on the patients' fecal samples (autologous).

Placebo/autologous FMT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Axial Spondyloarthritis according to the ASAS classification criteria
• Active disease defined as ASDAS ≥2.1 with elevated CRP ≥4 OR active inflammation on MRI within the last 3 months
• Onset of axial SpA within last 10 years
• Unsatisfactory relief of NSAIDs
• On stable immunomodulatory treatment (TNFi, IL17i or JAKi) the last 3 months

You may not qualify if:

• Planned dose adjustment or change in immunomodulatory treatment the next 90 days
• Disease or disorder with life expectancy of ≤5 years
• Severe immune deficiency (acquired, congenital og du to medication)
• Previous treatment with FMT
• Regular use of opioids with the exception of codeine and tramadol
• Any specific diagnosis that could explain or contribute to the patients back pain (e.g. tumor, fracture, infection or degenerative disease)
• Inflammatory spinal disease other than axSpA
• Severe psychiatric disorder, alcohol- or drug abuse
• Active inflammatory bowel disease
• Microscopic colitis, diverticulitis or ileus
• Active psoriasis
• Fibromyalgia
• Abdominal surgery excluding appendectomy, cholecystectomy, hysterectomy, caesarian section, sapling-ooforectomy and hernia surgery
• Malignant disease excluding basalioma and melanoma stage 1
• Conditions with expected necessary treatment with antibiotics during the study period, e.g. periodontitis end ischemic digital ulcers

Sponsors & Collaborators

• University Hospital of North Norway: lead
• Helse Nord: collaborator

Study Sites (1)

University Hospital North Norway

Tromsø, 9038, Norway

RECRUITING

Related Publications (6)

• Baraliakos X, Braun J. Spondyloarthritides. Best Pract Res Clin Rheumatol. 2011 Dec;25(6):825-42. doi: 10.1016/j.berh.2011.11.006.

  PMID: 22265264 RESULT

• Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020 Jun;30(6):492-506. doi: 10.1038/s41422-020-0332-7. Epub 2020 May 20.

  PMID: 32433595 RESULT

• Imdad A, Nicholson MR, Tanner-Smith EE, Zackular JP, Gomez-Duarte OG, Beaulieu DB, Acra S. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2018 Nov 13;11(11):CD012774. doi: 10.1002/14651858.CD012774.pub2.

  PMID: 30480772 RESULT

• Bazin T, Hooks KB, Barnetche T, Truchetet ME, Enaud R, Richez C, Dougados M, Hubert C, Barre A, Nikolski M, Schaeverbeke T. Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study. Sci Rep. 2018 Apr 3;8(1):5446. doi: 10.1038/s41598-018-23571-4.

  PMID: 29615661 RESULT

• Johnsen PH, Hilpusch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, Goll R. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):17-24. doi: 10.1016/S2468-1253(17)30338-2. Epub 2017 Nov 1.

  PMID: 29100842 RESULT

• Breban M, Beaufrere M, Glatigny S. The microbiome in spondyloarthritis. Best Pract Res Clin Rheumatol. 2019 Dec;33(6):101495. doi: 10.1016/j.berh.2020.101495. Epub 2020 Mar 12.

  PMID: 32173258 RESULT

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylitis, Ankylosing; Dysbiosis; Spondylarthritis; Spondylitis; Arthritis; Musculoskeletal Diseases; Spinal Diseases; Joint Diseases

Condition Hierarchy (Ancestors)

Spondylarthropathies; Bone Diseases; Ankylosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Diseases, Infectious; Infections

Central Study Contacts

Gunnstein Bakland, MD PhD

CONTACT

+4795860791; gunnstein.bakland@unn.no

Peter Johnsen, MD PhD

CONTACT

peter.holger.johnsen@unn.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A person will be responsible for the Randomization and Allocation (RAP) procedure, and will be the only person not blinded to randomization and treatment. This person will, however, be blinded for the patient´s identity.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Model Details: A blinded, randomized, placebo-controlled, parallel-group, single-center, superiority, phase III clinical trial. Participants randomized til active treatment will receive FMT from one of three donors. Allocation will be random in blocks of 9 (Donor A: Donor B : Donor C : Placebo 2:2:2:3).

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 11, 2024
• Study Start: June 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: March 1, 2026
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)