Effect of Butyrate Supplement on Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study is a pilot study to evaluate the safety and efficacy of administering butyrate supplement on rheumatoid arthritis patients. Ten participants will be included to receive butyrate supplement for 12 weeks. Changes of immune cell subtypes, markers of intestinal damage, intestinal flora and other laboratory indicators will be monitored.

Detailed Description
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This is a single center, uncontrolled, open-label study to assess the efficacy and safety of butyrate supplement plus standard therapy in rheumatoid arthritis(RA). The patients will be given 2 sodium butyrate capsules (containing 2400 mg of sodium butyrate) daily as supplemental therapy. The objective is to assess the effects of 12 weeks of sodium butyrate supplementation on intestinal inflammation and immune regulation in patients with RA, specifically changes in T-cell subtypes and biomarkers associated with intestinal injury. Clinical manifestations and other laboratory indices will also be monitored.

Official Title
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A Pilot Study to Evaluate Efficacy and Safety of Butyrate Supplement in the Treatment of Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Sodium Butyrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age at time of screening, weight≥35kg. Diagnosed with rheumatoid arthritis satisfying the 1987 American College of Rheumatology classification criteria. Stable treatment including DMARDs (Disease Modifying Anti-Rheumatic Drugs), the doses had been stable for at least 3 months before baseline Have given written informed consent Exclusion Criteria: Patient presenting or having a history of other inflammatory joint disease Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme Patient with significantly impaired bone marrow function or significant anemia, leucopenia or thrombocytopenia induced by other disease Patient with persistent infection or severe infection within 3 months before enrollment Patient with uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, terminal illness or other medical condition which would put the patient at risk to participate in the study according to the opinion of investigator Patient with cardiovascular, hepatic, neurological, endocrine, or other major systemic disease which may make implementation of the protocol or interpretation of the study results become difficult Patient who has severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome), with serum albumin < 30 g/L Patient who has moderate or severe impairment of renal function, as known by serum creatinine > 133μmol/L (or 1.5 mg/dl) Patient with impairment of liver function or persisting Alanine transaminase (ALT) or Aspartate aminotransferase (AST) elevations of more than 2-fold the upper limit of normal Patient with Known HIV positive status or positive serology for hepatitis B or C Pregnant or breastfeeding woman Women of childbearing potential Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 months with the washout procedure) Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or lymphoproliferative disease, or any patient who has received total lymphoid irradiation. Patient who enrolled in any other clinical trial involving off-label use of an investigational drug or device, or any other type of medical research Patient using any biologic agent such as anti-tumor necrosis factor, abciximab, Belimumab or rituximab within 3 months prior to the first dose of treatment. Patient whose BMI(body mass index) under 18.5 kg/m2 or more than 30 kg/m2 Patient with history of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: butyrate supplement<br>2 capsules butyrate supplement (containing 1200 mg of sodium butyrate ) once a day for 12 weeks Drug: sodium butyrate | Drug: Sodium Butyrate<br>* 2 capsules butyrate supplement once a day for 12 weeks<br>* Other names: TRI-Butyrin Supreme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-cell subtypes | Evaluating changes of percentage of T-cell subtypes, especially T regulatory cells (Treg) in Peripheral Blood | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum zonulin | Evaluating changes of zonulin concentration in serum. | 12 weeks | 
| serum occludin | Evaluating changes of occludin concentration in serum. | 12 weeks | 
| serum intestinal Fatty Acid Binding Protein | Evaluating changes of intestinal Fatty Acid Binding Protein(i-FABP) concentration in serum. | 12 weeks | 
| serum Lipopolysaccharide-binding protein | Evaluating changes of Lipopolysaccharide-binding protein concentration in serum. | 12 weeks | 
| serum tight junction protein 1 | Evaluating changes of tight junction protein 1 concentration in serum. | 12 weeks | 
| Faecal microbiome | Evaluating changes of faecal microbiome profiling by amplicon sequencing | 12 weeks | 
| Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28-ESR) | Evaluating changes of the DAS28 index, which was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and erythrocyte sedimentation rate value. A positive change in score indicates worsening, and a negative change indicates improvement. The score ranges from 0 to ca. 10 points, with > 5.1 indicating high disease activity, < 3.2 indicating low disease activity, and < 2.6 indicating clinical remission. Change from baseline to Week 12 will be used for the confirmation of therapeutic similarity. | 12 weeks | 
| Rate of participants with adverse effects associated with experimental drugs | Adverse effects include fever, rash, abnormal liver and kidney function, rate of new-onset infection and any abnormal measures associated with experimental drugs. | 12 weeks |