Effects of Administration of SCFA in Rheumatoid Arthritis Inadequate Responders

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 to Rheumatoid Arthritis (RA) patients with inadequate response to methotrexate (MTX). The study will include up to 35 participants to obtain a sample size of at least 25 participants taking the oral supplement. The researchers hypothesize 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, 1 month, and with an optional 2 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) Supplement in Rheumatoid Arthritis Inadequate Responders (EASi-RAIR)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Dietary Supplement: Butyrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA meeting 2010 ACR/EULAR for RA and/or treating MD diagnosis Inadequate response to MTX per treating MD at maximum tolerated dose. 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 antibiotic treatment (within 3 months of screening) at discretion of PI Current consumption of probiotics (within 3 months of screening) at discretion of PI 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 at discretion of PI 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: RA Patients who are Inadequate Responders to Current RA Treatment<br>Oral butyrate will be taken at 1000 mg three times daily with meals by RA patients who have active disease and are currently taking methotrexate (MTX) at prescriber's recommended dose. There will be no dose escalation of the study supplement. Clinical data to assess for adverse events, stool, urine samples and peripheral blood will be collected at baseline, 1 month, and with an optional 2-month time-point. | Dietary Supplement: Butyrate<br>* Participants will self-administer the oral Short Chain Fatty Acid (SCFA) Butyrate supplement three times daily with meals for up to 2 months. The minimum duration necessary for an evaluable participant will be 2 weeks of SCFA supplementation.<br>* Other names: Butyrate; butyric acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Microbiome Alpha Diversity | Measured by Shannon diversity index. | Baseline, Month 1 Post-Treatment Initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum SCFA Concentration | Measured via participant blood draws. | Baseline, Month 1 Post-Treatment Initiation | 
| Change in Fecal SCFA Concentration | Measured via participant stool samples. | Baseline, Month 1 Post-Treatment Initiation | 
| Change in Peripheral Regulatory T Cell Concentration | Measured via participant blood draws. | Up to Month 1 Post-Treatment Initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Short Chain Fatty Acid, Butyrate, Microbiome, Methotrexate