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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a supplement called butyrate to determine its effectiveness for people with rheumatoid arthritis (RA) who have not responded well to methotrexate. Researchers believe butyrate might improve the gut microbiome and immune responses. Participants will take the supplement and provide samples, such as blood and stool, to track any changes. This trial may suit individuals with RA who are taking methotrexate but still experience active symptoms. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance treatment options for RA.

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.

What prior data suggests that butyrate is safe for rheumatoid arthritis patients?

Research shows that butyrate, a substance produced by certain gut bacteria, can be safe for people with rheumatoid arthritis (RA). Studies indicate that butyrate capsules can help reduce disease symptoms and inflammation in RA patients, suggesting it might be a useful treatment option.

Regarding safety, earlier studies on butyrate supplements for RA found that patients generally tolerate the treatment well. The available research reported no serious side effects. It's important to remember that these findings come from smaller, initial studies that explored the safety and effectiveness of butyrate for RA.

Overall, while more research is needed to confirm these results, early studies suggest that taking butyrate is generally safe for people with RA. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for rheumatoid arthritis, which often include medications like methotrexate that target immune system functions, butyrate offers a novel approach by focusing on gut health. Butyrate is a short-chain fatty acid produced by gut bacteria, and it is known for its anti-inflammatory properties. Researchers are excited about butyrate because it could potentially reduce inflammation in a more natural way, by enhancing gut health and potentially providing relief with fewer side effects. This unique mechanism of action sets butyrate apart from current options, offering a promising new avenue for patients who don't respond adequately to existing treatments.

What evidence suggests that butyrate might be an effective treatment for rheumatoid arthritis?

Research has shown that butyrate, a type of fatty acid, might benefit people with rheumatoid arthritis (RA). One study found that butyrate lowered disease activity and reduced inflammation in RA patients. Another study discovered that butyrate supports the gut lining, which can help control immune responses related to RA. Additionally, people with RA often have lower levels of fatty acids like butyrate, and increasing these levels might ease symptoms. This trial will investigate the effects of butyrate for RA patients who do not respond adequately to current treatments, suggesting it could be a promising option for them. ^{1 5 6 7 8}

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

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11521846/

Butyrate: a bridge between intestinal flora and rheumatoid ...

Butyrate maintains intestinal barrier function by restraining intestinal immune responses in RA. The intestinal mucosal immune barrier ...

2.

science.org

science.org/doi/10.1126/sciadv.abm1511

Intestinal butyrate-metabolizing species contribute to ...

These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2589909025000516

Short-Chain Fatty Acids from Gut Microbiota Restore Th17/ ...

In RA patients, levels of SCFAs are typically reduced. Supplementation with SCFAs significantly ameliorates clinical manifestations in RA mouse ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11577678/

High-fat diet stimulated butyric acid metabolism dysbiosis, ...

In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and ...

5.

acrabstracts.org

acrabstracts.org/abstract/efficacy-safety-and-mechanism-of-butyrate-in-the-treatment-of-rheumatoid-arthritis-ra/

Efficacy, Safety and Mechanism of Butyrate in the ...

Conclusion: Butyrate capsules are safe and effective for RA, reducing disease activity and inflammation, and suggesting new dietary or microbial therapy options ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05576597

Effect of Butyrate Supplement on Rheumatoid Arthritis

This study is a pilot study to evaluate the safety and efficacy of administering butyrate supplement on rheumatoid arthritis patients.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352396420302887

Microbiota-derived butyrate limits the autoimmune ...

Thus, the raising luminal butyrate during this phase may reduce the risk of relapses in patients with RA. We also detected a reduction tendency of luminal ...

8.

cdek.pharmacy.purdue.edu

cdek.pharmacy.purdue.edu/trial/NCT05576597/

Trial | NCT05576597

This study is a pilot study to evaluate the safety and efficacy of administering butyrate supplement on rheumatoid arthritis patients.