Effects of Administration of SCFA in Rheumatoid Arthritis Inadequate Responders (EASi-RAIR)

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)

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Dietary supplement: Butyrate

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health Orthopedic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of RA meeting 2010 ACR/EULAR for RA and/or treating MD diagnosis
2. Inadequate response to MTX per treating MD at maximum tolerated dose.
3. Able and willing to provide written informed consent prior to any study specific procedures
4. Age 18 years and above at time of enrollment
5. Subjects not excluded based on race or ethnicity

Exclusion Criteria:

1. Participants who are pregnant or are currently breastfeeding
2. History of sensitivity to study compound or any of their excipients
3. Previous intolerance to SCFA or related compounds
4. Current antibiotic treatment (within 3 months of screening) at discretion of PI
5. Current consumption of probiotics (within 3 months of screening) at discretion of PI
6. Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy)
7. Renal failure (eGFR <30 or requiring dialysis) by history
8. History of other autoimmune disease at discretion of PI
9. Current immunodeficiency state (e.g., cancer, HIV, others)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RA Patients who are Inadequate Responders to Current RA Treatment; 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; 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.; Other Names: Butyrate; butyric acid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Arthritis Foundation
• Investigators: Principal Investigator: Jose Scher, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): February 20, 2025
• Study Completion (Actual): February 20, 2025

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Methotrexate; Rheumatoid Arthritis; Butyrate; Short Chain Fatty Acid
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Butyric Acid; Butyrates
• Other Study ID Numbers: 22-01526

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: [Rebecca.blank@nyulangone.org]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Rebecca.blank@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No