Efficacy of Probiotics for NSAID-induced Enteropathy in Arthritis Patients

Study Overview
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Brief Summary
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This study aimed to investigate the efficacy of probiotics as a preventive agent for NSAID-induced enteropathy. Arthritis patients are randomly divided into probiotic and placebo groups, and the drug is administered for eight weeks. Before and after drug administration, the patient's symptoms/degree of small bowel injuries on capsule endoscopy/microbiome composition and diversity were investigated.

Detailed Description
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Background: Due to aging, there are many long-term users of NSAIDs, increasing enteropathy. The prophylactic effect of misoprostol, which is currently used, has not been proven, and misoprostol's long-term compliance and safety remain questionable. Rebamipide shows insignificant effects in both treatment and prophylaxis. Probiotics have been reported to affect enteropathy in animal and human studies. However, there needs to be more verification studies, and there needs to be confirmatory studies on the importance of the microbiome in the small bowel. However, it is expected that there will be fewer complications and less patient resistance, resulting in higher drug compliance. Purpose: To identify the efficacy of probiotics on NSAID-induced enteropathy in arthritis patients by capsule endoscopy and questionnaire, and to analysis the composition and diversity of the microbiome Design: Double-blinded randomized controlled, pilot study Participant: Patients diagnosed with osteoarthritis and starting NSAIDs Methods: Randomly administering Probiotics or Placebo for eight weeks and comparing before and after administration in arthritis patients Survey of patient symptoms for enteropathy Recovery of small bowel mucosal injuries in capsule endoscopy Analysis of the composition and diversity of the microbiome Adverse events Outcome Primary outcome: To assess whether probiotics can reduce small bowel injuries caused by NSAIDs Secondary outcome: To investigate whether probiotics can reduce gastrointestinal symptoms caused by NSAIDs To identify the improvement of arthritis symptoms To examine whether the distribution of the microbiome can be converted into beneficial bacteria by administering probiotics

Official Title
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Efficacy of Probiotics for Non-steroidal Anti-inflammatory Drug-induced Enteropathy in Arthritis Patients: A Double-blinded Pilot Randomized Controlled Trial

Conditions
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Osteoarthritis

Intervention / Treatment
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* Combination Product: Probiotics capsule
* Combination Product: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with axial SpA who meet the 2009 ASAS criteria or osteoarthritis diagnosed by hand or foot x-rays Exclusion Criteria: History of taking NSAIDs or antibiotics within the last month Those who have been taking probiotics, steroids, or immunosuppressants for a long time Abdominal surgical history (exception: appendectomy, cholecystectomy) History of gastrointestinal malignant disease Abnormal findings requiring drug treatment or surgery in upper gastrointestinal endoscopy (e.g., digestive cancer, acute peptic ulcer, etc.) Hemorrhagic disease Anemia with hemoglobin less than 10 g/dL Past NSAIDs drug side effects (allergy)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Probiotics group vs. Placebo group
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotics arm<br>Probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) per oral, three times a day, for 8 weeks | Combination Product: Probiotics capsule<br>* Subjects will take a probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) three times a day for 8 weeks in combination with NSAIDs<br>|
| Placebo Comparator: Placebo arm<br>Placebo capsule in the same form as probiotics, per oral, three times a day, for 8 weeks | Combination Product: Placebo capsule<br>* Subjects will take a placebo capsule identical in shape and size to probiotics capsule three times a day for 8 weeks in combination with NSAIDs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the small bowel injuries on capsule endoscopy | Changes in the number of ulcers/erosions in the small bowel mucosa on capsule endoscopy before and after taking the NSAIDs and Probiotics/Placebo | From enrollment to the end of treatment at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Questionnaire Scores | Change from Baseline in Gastrointestinal Symptom Rating Scale Questionnaire Scores at 8 Weeks Symptoms: Pain or discomfort in upper abdomen, Heartburn, Acid reflux, Hunger pangs, Nausea, Rumbling, Bloating, Passing gas, Constipation, Diarrhea, Loose stool, Hard stool, Urgent bowel movement, Sensation of not completely emptying bowel Scoring: Each of the 15 items is scored from 0 to 6 points, with the highest score being 45 points and the lowest being 0 points. A score of 0 means no gastrointestinal symptoms, and a higher score indicates a more frequent occurrence of the corresponding symptoms. | From enrollment to the end of treatment at 8 weeks | 
| Change From Baseline in Symptom Scores on the Western Ontario and McMaster Universities (WOMAC) Arthritis Index | WOMAC index: Descending stairs, Ascending stairs, Rising from sitting, Standing, Bending to floor, Walking on flat surface, Getting in/out of car, Going shopping, Putting on socks, Lying in bed, Talking off socks, Rising from bed, Getting in/out of bath, Sitting, Getting on/off toilet, Heavy domestic duties, Light domestic duties Each of the 24 items is scored from 0 to 4 points, with the highest score being 96 points and the lowest being 0 points. A score of 0 means no symptoms and a higher score indicates more severe symptoms of the corresponding symptoms. | From enrollment to the end of treatment at 8 weeks | 
| Change From Baseline in Symptom Scores on the Knee Injury and Osteoarthritis Outcome Scores (KOOS) Questionnaire at 8 Weeks | Assessment of KOOS: Daily living, Sports and recreational activities, Pain, Quality of life, Symptoms and stiffness Each of the 42 items is scored from 0 to 4 points, with the highest score being 168 points and the lowest being 0 points. A score of 0 means no symptoms, and a higher score indicates more severe and frequent symptoms of the corresponding symptoms. | From enrollment to the end of treatment at 8 weeks | 
| Changes in the gut microbiome through Next Generation Sequencing | Changes in composition and diversity of gut microbiota through stool samples Changes in microbial genome composition | From enrollment to the end of treatment at 8 weeks |