A Pilot Proof of Concept Study of the Effects of Administration of SCFA in Rheumatoid Arthritis (EASi-RA)

Study Overview
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Brief Summary
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This study is a pilot, proof of concept study to determine the effects of administering an oral short chain fatty acid (SCFA) supplement along with methotrexate as first line treatment of new onset rheumatoid arthritis (NORA) patients. Up to 50 participants will be included to obtain a sample size of at least 16 participants taking the oral supplement. The study team hypothesizes that oral SCFA will change the participants' gut microbiome and regulatory immune responses. Clinical data to assess for adverse events, stool, urine samples and peripheral blood will be collected at baseline, 2 and 4 months with an optional 6-month time point. Fecal microbiome will be analyzed. Adaptive immune responses will be analyzed from participant blood samples.

Official Title
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A Pilot Proof of Concept Study of the Effects of Administration of a Short Chain Fatty Acid (SCFA) in Rheumatoid Arthritis (EASi-RA)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Dietary Supplement: Short Chain Fatty Acids (SCFA) Dietary Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis of rheumatoid arthritis (RA) (<6 months) meeting 2010 ACR/EULAR for RA Scheduled to begin treatment with methotrexate at any dose as standard medical care Able and willing to provide written informed consent prior to any study specific procedures Age 18 years and above at time of enrollment Subjects not excluded based on race or ethnicity Exclusion Criteria: Participants who are pregnant or are currently breastfeeding History of sensitivity to study compound or any of their excipients Previous intolerance to SCFA or related compounds Current (within 3 months of screening) treatment with csDMARDs Current or past (ever) treatment with biologic therapies (including but not limited to anti-TNF, anti-IL-17, anti-IL-12/23) Current antibiotic treatment (within 3 months of screening) Current consumption of probiotics (within 3 months of screening) Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy) Renal failure (eGFR <30 or requiring dialysis) by history History of other autoimmune disease Current immunodeficiency state (e.g., cancer, HIV, others)

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: New Onset Rheumatoid Arthritis (NORA) Patient<br>NORA patients receiving methotraxate as first line therapy (standard of care) will take additional oral SCFA supplementation for the purposes of the study. | Dietary Supplement: Short Chain Fatty Acids (SCFA) Dietary Supplement<br>* Butryate 1000 mg three times daily will be used in this study.<br>* Other names: Butyrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percentage of Circulating T Regulatory Cells (Treg) |  | Baseline, Visit 2 (60 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut microbiota composition after SCFA supplementation |  | Baseline, Visit 2 (60 days), Visit 3 (120 days), Visit 4 (180 days) | 
| Change in Fecal SCFA Concentration after SCFA supplementation |  | Baseline, Visit 2 (60 days), Visit 3 (120 days), Visit 4 (180 days) | 
| Change in Interleukin-10 (IL-10) Production Levels after SCFA Supplementation |  | Baseline, Visit 2 (60 days), Visit 3 (120 days), Visit 4 (180 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short Chain Fatty Acid (SCFA), Butyrate, Gut Microbiome