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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests butyrate enemas as a treatment for children and teens with mild to moderate ulcerative colitis, a condition that inflames the colon. Butyrate, produced by beneficial gut bacteria, might help reduce this inflammation. The trial aims to evaluate the effectiveness and safety of these enemas. It is suitable for individuals aged 7 to 21 who have ulcerative colitis and have not received any UC treatment in the past four weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that butyrate is likely to be safe for humans?

Research has shown that butyrate is usually safe for children with inflammatory bowel diseases like ulcerative colitis. Studies have found that sodium butyrate does not cause harmful effects and can help reduce inflammation in these conditions. While butyrate plays a crucial role in maintaining gut health, few direct studies have examined its ability to heal the gut lining in humans. However, it has demonstrated protective effects in patients with inflammatory bowel disease, suggesting it may be safe for use in treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about butyrate therapy for pediatric ulcerative colitis because it offers a unique approach compared to the standard treatments like aminosalicylates, corticosteroids, and immunosuppressants. Butyrate, a short-chain fatty acid, is naturally produced in the gut and plays a key role in maintaining intestinal health. Unlike current treatments that primarily focus on reducing inflammation, butyrate may help restore the gut lining and promote healing by enhancing the health of colon cells. Additionally, the delivery method via enemas allows for direct application to the affected area, potentially offering more targeted relief and fewer systemic side effects.

What evidence suggests that butyrate might be an effective treatment for pediatric ulcerative colitis?

Research has shown that butyrate, a substance produced by the gut, can help manage ulcerative colitis in children. One study found that 81.82% of children taking sodium butyrate experienced remission, meaning their symptoms decreased, by week 12. This indicates that many children felt better after using it for a few months. Other research suggests that sodium butyrate reduces inflammation in children with ulcerative colitis and Crohn's disease. It is also well-tolerated, meaning it usually doesn't cause adverse side effects. This trial will evaluate the effectiveness of butyrate enemas administered once daily for twelve weeks, suggesting that butyrate might help children with ulcerative colitis feel better. ^{1 2 6 7 8}

Who Is on the Research Team?

Sonia Michail, MD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40566555/

Clinical Efficacy of Sodium Butyrate in Managing Pediatric ... Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate, 81.82%; 21 patients in Group B with ...

2. mdpi.com mdpi.com/2075-1729/15/6/902

Clinical Efficacy of Sodium Butyrate in Managing Pediatric ... Sodium butyrate is a well-tolerated product with no adverse effects that reduces inflammatory activity in children with Crohn's disease and ulcerative colitis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9414716/

Sodium Butyrate Effectiveness in Children and ... Oral butyric acid supplementation has been shown to reduce dysbiosis in UC patients [13]. On the other hand, there are not many clinical trials ...

4. researchgate.net researchgate.net/publication/392389792_Clinical_Efficacy_of_Sodium_Butyrate_in_Managing_Pediatric_Inflammatory_Bowel_Disease

Clinical Efficacy of Sodium Butyrate in Managing Pediatric ... Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate, 81.82%; 21 patients in Group B with ...

5. omicsdi.org omicsdi.org/dataset/biostudies-literature/S-EPMC9414716

S-EPMC9414716 - Sodium Butyrate Effectiveness in ... The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10221771/

Gut Microbial Metabolite Butyrate and Its Therapeutic Role in ... Butyrate, a gut microbial metabolite, plays a crucial role in regulating immune function, epithelial barrier function, and intestinal homeostasis.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0261561422003843

Butyrate's role in human health and the current progress ... There are no direct studies of butyrate on mucosal healing in humans, although studies in IBD patients suggest that butyrate has a protective effect (see IBD ...

8. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-022-02191-3

Characterization of short-chain fatty acids in patients with ... UC patients had significantly decreased concentrations of total SCFAs, acetate, propionate, and valerate compared with healthy subjects.