Butyrate for Rheumatoid Arthritis

(EASi-RAIR Trial)

Overseen By Rebecca B. Blank, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: Methotrexate

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Pregnancy, Breastfeeding, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 month

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a supplement with small molecules for RA patients who don't improve with standard treatment. The supplement aims to change gut bacteria and improve immune responses. These molecules are involved in the body's inflammatory response and immunity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response to methotrexate, which suggests you may continue taking it. Please consult with the trial coordinators for more details.

How does butyrate treatment differ from other rheumatoid arthritis treatments?

Butyrate is unique because it is a short-chain fatty acid produced by gut bacteria that helps reduce inflammation in rheumatoid arthritis by promoting regulatory T cells (which help control the immune response) and inhibiting harmful immune cells. Unlike traditional treatments, it works by balancing gut microbiota and targeting specific enzymes involved in inflammation. ^{1 2 3 4 5}

Who Is on the Research Team?

Rebecca Blank, MD, PhD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Rheumatoid Arthritis who haven't had enough relief from methotrexate. It's not for those with severe liver problems, kidney failure, immune deficiencies like cancer or HIV, pregnant or breastfeeding women, previous SCFA intolerance, recent antibiotic or probiotic use.

Inclusion Criteria

Able and willing to provide written informed consent prior to any study specific procedures

Subjects not excluded based on race or ethnicity

I have been diagnosed with rheumatoid arthritis by my doctor.

Exclusion Criteria

I have been on antibiotics in the last 3 months, as decided by my doctor.

Participants who are pregnant or are currently breastfeeding

History of sensitivity to study compound or any of their excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an oral short-chain fatty acid (SCFA) supplement to assess changes in gut microbiome and immune responses

1 month

Baseline, 1 month, optional 2 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Butyrate

Trial Overview The study tests if an oral supplement of short-chain fatty acids (SCFAs) can help people with Rheumatoid Arthritis by changing their gut bacteria and immune response. Up to 35 participants will take the supplement alongside regular blood, stool, and urine tests over up to two months.

How Is the Trial Designed?

Group I: RA Patients who are Inadequate Responders to Current RA Treatment Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Arthritis Foundation

Collaborator

Trials

36

Recruited

46,500+

Published Research Related to This Trial

Butyrate effectively inhibits the production of tumor necrosis factor alpha (TNFalpha) in macrophage-like synoviocytes from rheumatoid arthritis patients and human peripheral monocytes, suggesting its potential as a therapeutic agent for RA.

The mechanism by which butyrate suppresses TNFalpha involves enhancing the degradation of its mRNA through the action of the AU-rich element-binding protein TIS11B, indicating a novel way to regulate inflammatory responses at the genetic level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrate suppresses tumor necrosis factor alpha production by regulating specific messenger RNA degradation mediated through a cis-acting AU-rich element. Fukae, J., Amasaki, Y., Yamashita, Y., et al.[2022]

Rheumatoid arthritis (RA) patients show a significant deficiency in butyrate-producing gut bacteria and an excess of butyrate consumers, particularly in those with positive ACPA, indicating a potential imbalance in their intestinal microbiome.

Butyrate has been shown to promote regulatory T cells (Tregs) and suppress pro-inflammatory responses, suggesting that dietary butyrate supplementation could offer anti-inflammatory benefits and serve as a potential therapeutic strategy for RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis. He, J., Chu, Y., Li, J., et al.[2022]

Short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate are found at lower levels in rheumatoid arthritis (RA) patients and are linked to increased regulatory B cells (Bregs), which help modulate the immune response.

Administering SCFAs before the onset of arthritis in mice improved symptoms and increased Bregs, but these effects depended on FFA2 receptors, suggesting a specific mechanism through which SCFAs can potentially alleviate RA symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-chain fatty acids regulate B cells differentiation via the FFA2 receptor to alleviate rheumatoid arthritis. Yao, Y., Cai, X., Zheng, Y., et al.[2022]

In an animal model of rheumatoid arthritis, treatment with butyrate significantly reduced arthritis scores and incidence, indicating its potential as a therapeutic agent.

Butyrate works by inhibiting specific histone deacetylases (HDACs) in immune cells, which helps regulate immune responses and maintain a balance between pro-inflammatory and anti-inflammatory cells, particularly through the production of interleukin-10 (IL-10).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of Rheumatoid Inflammation by Sodium Butyrate Through Reciprocal Targeting of HDAC2 in Osteoclasts and HDAC8 in T Cells. Kim, DS., Kwon, JE., Lee, SH., et al.[2019]

In a mouse model of rheumatoid arthritis, butyrate significantly reduced inflammation by inhibiting pro-inflammatory cytokines like IL-1β, IL-6, and IL-17A, while promoting the anti-inflammatory cytokine IL-10.

Butyrate's beneficial effects were linked to its ability to enhance the differentiation of regulatory T cells (Treg) and suppress Th17 cells, suggesting a mechanism that could be targeted for new RA therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis. Hui, W., Yu, D., Cao, Z., et al.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Butyrate suppresses tumor necrosis factor alpha production by regulating specific messenger RNA degradation mediated through a cis-acting AU-rich element. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Short-chain fatty acids regulate B cells differentiation via the FFA2 receptor to alleviate rheumatoid arthritis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Attenuation of Rheumatoid Inflammation by Sodium Butyrate Through Reciprocal Targeting of HDAC2 in Osteoclasts and HDAC8 in T Cells. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis. [2019]