Butyrate Therapy for Pediatric Ulcerative Colitis

Overseen By Sonia Michail, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital Los Angeles

Disqualifiers: Infectious colitis, Pregnancy, others

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

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Butyrate is an important metabolite produced by the gut microbiome and has been shown as a helpful therapy in ulcerative colitis. This is a feasibility study to determine the efficacy of butryate enemas in pediatric ulcerative colitis.

Will I have to stop taking my current medications?

The trial requires that you stop any ulcerative colitis therapy at least 4 weeks before starting the study medication.

What data supports the effectiveness of the treatment Butyrate for pediatric ulcerative colitis?

Research shows that butyrate, a short-chain fatty acid, can help maintain remission and improve symptoms in ulcerative colitis patients. In one study, patients using butyrate had better outcomes compared to those on standard treatment alone, suggesting it may be a helpful addition to existing therapies. ^{1 2 3 4 5}

How is butyrate treatment different from other treatments for pediatric ulcerative colitis?

Butyrate treatment is unique because it involves using a naturally occurring short-chain fatty acid that helps maintain gut health and integrity, and it can be administered in various ways, such as orally, intrarectally, or intraperitoneally. This treatment is different from standard therapies as it focuses on increasing butyrate levels in the gut, which can be achieved through dietary changes or direct administration, potentially offering a novel approach to managing ulcerative colitis. ^{1 5 6 7 8}

Research Team

Sonia Michail, MD

Principal Investigator

Children's Hospital Los Angeles

Eligibility Criteria

This trial is for children and young adults aged 7-21 with mild to moderate ulcerative colitis. Participants must not be pregnant, should not have received ulcerative colitis therapy within the last 4 weeks, and must not have infectious colitis.

Inclusion Criteria

I am between 7 and 21 years old with mild to moderate ulcerative colitis.

Exclusion Criteria

Pregnancy

I haven't had ulcerative colitis treatment in the last 4 weeks.

I have had infectious colitis in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Butyrate enemas are administered once daily for twelve weeks to children with mild to moderate ulcerative colitis

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Butyrate

Trial Overview The study is testing butyrate enemas as a treatment for pediatric ulcerative colitis. Butyrate is a compound produced in the gut that may help manage this condition. The trial aims to assess how effective this approach could be.

Participant Groups

Group I: open label intervention arm Experimental Treatment 1 Intervention

Butyrate enemas will be administered once daily for twelve weeks.

Who Is Running the Clinical Trial?

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Findings from Research

In a study of nine patients with distal ulcerative colitis who did not respond to standard treatments, a combination of sodium butyrate and 5-ASA administered rectally led to significant clinical and endoscopic improvements in seven patients.

The clinical benefits were typically observed within two weeks of starting the treatment, suggesting that this combined therapy may work faster than butyrate alone and could enhance the effectiveness of existing treatments for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate. Vernia, P., Cittadini, M., Caprilli, R., et al.[2019]

In a study of 47 patients with active distal ulcerative colitis, treatment with rectal enemas containing butyrate, a short-chain fatty acid, showed a significant reduction in disease activity after eight weeks, similar to saline placebo and other treatments.

While all treatments improved disease activity, butyrate enemas resulted in fewer affected colonic segments compared to placebo, suggesting a potential benefit of short-chain fatty acids in managing ulcerative colitis, although further research with more participants is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Scheppach, W.[2019]

In a study of 10 patients with refractory distal ulcerative colitis, 50% showed clinical improvement after 6 weeks of treatment with short chain fatty acid enemas, indicating potential efficacy for this therapy.

No side effects were reported during the treatment, suggesting that short chain fatty acids may be a safe option for patients who have not responded to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas. Patz, J., Jacobsohn, WZ., Gottschalk-Sabag, S., et al.[2017]

In a pilot study involving 30 patients with mild to moderate ulcerative colitis, oral sodium butyrate was found to be safe and well tolerated, with no reported side effects during the six-week treatment period.

The combination of oral sodium butyrate and mesalazine showed a trend towards better clinical improvement compared to mesalazine alone, suggesting that butyrate may enhance the efficacy of standard treatment for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study. Vernia, P., Monteleone, G., Grandinetti, G., et al.[2019]

In a study of 39 patients with ulcerative colitis, those receiving oral microencapsulated sodium butyrate (BLM) as an add-on therapy achieved a higher therapeutic success rate (83.3%) compared to those on standard mesalamine alone (47.6%), indicating BLM's efficacy in maintaining remission.

Patients treated with BLM also showed significant improvements in residual symptoms and a notable reduction in inflammatory markers (faecal calprotectin), suggesting that BLM could be a beneficial adjunct treatment for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Usefulness of Microencapsulated Sodium Butyrate Add-On Therapy in Maintaining Remission in Patients with Ulcerative Colitis: A Prospective Observational Study. Vernero, M., De Blasio, F., Ribaldone, DG., et al.[2020]

In a 3-month pilot trial with 22 patients suffering from quiescent ulcerative colitis, adding 60 g of oat bran daily significantly increased fecal butyrate levels by 36%, indicating a safe dietary method to enhance butyrate production.

No patients experienced a relapse of colitis during the study, and those with initial abdominal pain reported significant improvement, suggesting that a diet high in oat bran may be beneficial for managing symptoms in ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. Hallert, C., Björck, I., Nyman, M., et al.[2019]

In a study involving 30 rats, butyrate treatment significantly reduced the incidence and size of tumors in rats with experimental colitis, suggesting its protective effects against colon cancer development.

Butyrate therapy restored transglutaminase activity in the colonic tissue, indicating a potential mechanism by which it may help decrease the risk of cancer in patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model. D'Argenio, G., Cosenza, V., Delle Cave, M., et al.[2019]

Intraperitoneal administration of butyrate significantly reduces the lesions caused by acetic acid-induced ulcerative colitis in rats, showing the highest effectiveness compared to intrarectal and oral routes.

All forms of butyrate administration (intraperitoneal, intrarectal, and oral) improved symptoms and histological damage associated with ulcerative colitis, but intraperitoneal delivery was the most potent, suggesting a potential for systemic treatment in colorectal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats. Malago, JJ., Sangu, CL.[2018]

References

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

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate. [2019]

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

Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. [2019]

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

Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas. [2017]

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

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Usefulness of Microencapsulated Sodium Butyrate Add-On Therapy in Maintaining Remission in Patients with Ulcerative Colitis: A Prospective Observational Study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. [2019]

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

Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model. [2019]

8. China pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats. [2018]