Clinical trial NCT06451588: Fecal Microbiota Transplantation in Axial Spondyloarthritis
Official title: Donor Versus Autologous Fecal Microbiota Transplantation for Axial Spondyloarthritis: a Double Blind, Placebo-Controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
Collaborators: name: Helse Nord
First posted: 2024-06-11
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

Detailed description: Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints (SIJ) and the spine.

The approach to treatment of axSpA is a combination of patient education, with a focus on exercise and lifestyle, and a medical treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medical treatment, providing symptom relief for a large portion of the patients. For patients with inadequate response, or intolerance, to NSAIDs, biological (TNFi and IL17i) or targeted synthetic (JAKi) disease modifying drugs (b/ts-DMARDs) are considered a second-line treatment option and provide excellent efficacy for many patients. However, a substantial portion of the patients experience active disease despite this second-line therapy.

The cause of the disease is multifactorial, and both genetic and environmental factors contribute in the pathogenesis. Patients with axSpA have a higher prevalence of inflammatory bowel disease (IBD) than the background population, i.e. Crohn's disease and ulcerative colitis. However, inflammation in the gut is also demonstrated in 50-70% of patients without symptoms of IBD, and this inflammation is believed to be of importance in the development of the disease.

The human gut microbiota is the collection of microbes in the intestines. The composition of the microbiota is the result of many factors and have evolved over time to form a mutually beneficial relationship to both humans and microorganisms. Normally there is a balance and a stability in this composition, but in many conditions an imbalance, termed dysbiosis, has been demonstrated. This is also the case in axSpA, and the extent of this dysbiosis also relates to disease activity and to response to therapy.

Fecal microbiota transplantation (FMT) is a method used to alter the microbiota composition by transferring microbes from a healthy individual to a recipient. In several conditions this has both proven the ability to alter the microbiota and to provide symptom relief , e.g. clostridium difficile infections, ulcerative colitis and irritable bowel syndrome.

Given the potential role of the microbiota in the pathogenesis of axSpA, we wish to evaluate whether replacing the microbiota in patients with inadequate response to biologic therapy with FMT can be efficacious in providing a state of inactive disease and symptom relief.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Treatment with antibiotics 12 weeks prior to study entry
* Pregnancy, lactation or planned pregnancy within the next 3 months
* Contraindications for rectal catheter insertion
* Planned rehabilitation program the next 90 days
* Limited ability to comply with protocol requirements, including biobank participation

Primary outcomes:
measure: Minimal Clinically Important Improvement
timeFrame: 90 days
Secondary outcomes:
measure: Adverse events
timeFrame: Day 0-90 and day 91-365
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS)20
timeFrame: baseline, day 30, day 60 and day 90
measure: Bath Ankylosing Spondylitis Disease Activity Index
timeFrame: baseline, day 30, day 60 and day 90
measure: Bath Anykylosing Spondylitis Funtional Index
timeFrame: baseline, day 30, day 60 and day 90
measure: Patient global assessment
timeFrame: baseline, day 30, day 60 and day 90
measure: VAS spinal pain
timeFrame: baseline, day 30, day 60 and day 90
measure: Modified Fatigue Impact Scale
timeFrame: baseline and day 90
measure: RAND-36
timeFrame: baseline and day 90
measure: Maastricht Ankylosing Spondylitis Enthesitis Score
timeFrame: baseline and day 90
measure: The 66/68 Joint Count Score
timeFrame: baseline and day 90
measure: Bath Ankylosing Spondylitis Metrology Index
timeFrame: baseline and day 90
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS)40
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: Bath Ankylosing Spondylitis Disease Activity Index
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: Bath Anykylosing Spondylitis Funtional Index
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: Patient global assessment
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: VAS spinal pain
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: Modified Fatigue Impact Scale
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
measure: RAND-36
timeFrame: baseline and day 30, day 60, day 90, day 180, day 270 and day 365
Other outcomes:
measure: Exploratory endpoint
timeFrame: baseline and day 90
measure: Exploratory endpoint
timeFrame: baseline
Locations:
city: Tromsø
country: Norway
facility: University Hospital North Norway
Study officials:
References:
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