Rifaximin + Hydrogen Breath Test for IBS-D

Overseen By William Chey, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must not be taking: Antibiotics, Probiotics, P-glycoprotein inhibitors

Disqualifiers: Pregnancy, Diabetes, Celiac, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

175 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for individuals with diarrhea-predominant Irritable Bowel Syndrome (IBS-D). Participants will take rifaximin, a medication believed to alleviate IBS-D symptoms, and undergo hydrogen breath tests to assess the treatment's effects. The trial seeks individuals experiencing IBS-D symptoms such as frequent diarrhea and abdominal pain, who have not taken antibiotics in the past month. Participants will also complete online surveys and provide biological samples during the study. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop using antibiotics and probiotics before participating. Additionally, you cannot use P-glycoprotein inhibitors (a type of medication that affects how drugs are absorbed in the body) during the study.

What is the safety track record for Rifaximin and the Hydrogen Breath Test?

Research shows that rifaximin is generally safe for people. Studies have found that patients with diarrhea-predominant irritable bowel syndrome (IBS-D) who took rifaximin tolerated it well. For IBS-D, the usual dose is 550 mg three times a day for 14 days, matching the dose used in the study. Many patients have used this treatment without serious side effects.

The most common side effects include headache, nausea (feeling sick to the stomach), and increased liver enzymes, which are proteins that assist with chemical reactions in the body. These side effects are usually mild and resolve quickly. The FDA has approved rifaximin for treating IBS-D, indicating its safety for many people. Always consult a healthcare provider about any concerns before starting a new treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Rifaximin is unique because it targets the gut bacteria associated with IBS-D (Irritable Bowel Syndrome with Diarrhea), using an antibiotic approach that differs from the common symptomatic treatments like loperamide or antispasmodics. Unlike these traditional options, Rifaximin is a non-absorbable antibiotic, meaning it acts specifically in the gut without significantly affecting the rest of the body. Researchers are excited because it offers a targeted treatment option that can potentially reset the gut microbiota balance, providing relief from symptoms and possibly longer-lasting benefits after the treatment period ends.

What evidence suggests that Rifaximin might be an effective treatment for IBS-D?

Research has shown that rifaximin effectively treats diarrhea-predominant irritable bowel syndrome (IBS-D). In one study, 69% of patients taking rifaximin reported improvement. Another study found that two weeks of rifaximin treatment significantly reduced stomach pain and diarrhea in adults with IBS-D. A meta-analysis, which combines results from several studies, confirmed that rifaximin is safe and effective for treating IBS-D. These findings suggest that rifaximin is a reliable option for managing IBS-D symptoms. Participants in this trial will receive rifaximin along with hydrogen breath tests to further evaluate its effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

William Chey, M.D.

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with Irritable Bowel Syndrome predominant diarrhea (IBS-D) who meet specific criteria of abdominal pain and diarrhea, have kept a symptom diary for at least 5 days without rescue meds, and fit the Rome IV Diagnostic Criteria. It's not open to those with certain other diseases like inflammatory bowel disease or diabetes, recent GI surgery patients, severe liver issues, pregnant or lactating women, anyone who has taken antibiotics recently or uses probiotics.

Inclusion Criteria

IBS-D (Rome IV Diagnostic Criteria)

My abdominal pain and diarrhea are manageable.

I kept a health diary for 5 days without needing emergency meds.

Exclusion Criteria

I have inflammatory bowel disease, diabetes, systemic sclerosis, or celiac disease.

Pregnant women or planning on becoming pregnant while in the study, or lactating women while in the study

I am not taking any medications like Cyclosporine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Daily online surveys

Treatment

Participants receive a 14-day course of rifaximin and complete hydrogen breath tests

2 weeks

In-person visits for breath tests and biological sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of abdominal pain and stool consistency

4 weeks

Weekly assessments

Extended Follow-up

Continued monitoring of symptoms and quality of life measures

8 weeks

Assessments at weeks 4, 8, and 12

What Are the Treatments Tested in This Trial?

Interventions

• Hydrogen Breath Test
• Rifaximin

Trial Overview The study tests if hydrogen breath testing can predict how well people with IBS-D respond to rifaximin treatment. Participants will take rifaximin and undergo glucose and lactulose hydrogen breath tests while providing biological samples and completing online surveys about their symptoms.

How Is the Trial Designed?

Group I: Rifaximin and breath tests Experimental Treatment 2 Interventions

Rifaximin 550mg three times a day for 14 days. Breath tests (glucose and lactulose) will be completed prior to Rifaximin treatment and at week 13 of the study.

Rifaximin is already approved in United States, Canada, European Union, India for the following indications:

Approved in United States as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in Canada as Zaxine for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in European Union as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in India as Ciboz and Xifapill for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Commonwealth Diagnostics International, Inc.

Collaborator

Trials

1

Recruited

110+

Published Research Related to This Trial

In a study of 93 adults with irritable bowel syndrome with diarrhea (IBS-D), a positive lactulose breath test (LBT) before treatment was associated with a significantly higher response rate to rifaximin, with 59.7% of those with positive LBT responding compared to only 25.8% of those with negative LBT.

Patients whose LBT results normalized after rifaximin treatment had the highest response rate of 76.5%, suggesting that rifaximin may work by modulating the gut microbiome, although LBT results after treatment did not correlate with clinical response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea. Rezaie, A., Heimanson, Z., McCallum, R., et al.[2023]

In a study of 443 patients, 53 were diagnosed with small intestinal bacterial overgrowth (SIBO) based on breath tests, and rifaximin was found to be an effective treatment, with a response rate of 47.4% for hydrogen-positive SIBO and 80% for those with both hydrogen and methane positivity.

Rifaximin, administered at 550 mg three times daily for 14 days, is highlighted as the most commonly prescribed antibiotic for SIBO, showing significant potential for symptom relief in patients with SIBO, particularly those with hydrogen-positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential usage of rifaximin for the treatment of hydrogen-positive smallintestinal bacterial overgrowth. Barkin, JA., Keihanian, T., Barkin, JS., et al.[2020]

In a study of 19 non-IBS patients with symptoms suggestive of small intestinal bacterial overgrowth (SIBO), rifaximin treatment did not effectively normalize lactulose-H2 breath tests, with only 42.1% showing any improvement.

Despite the lack of efficacy in breath test normalization, rifaximin was well-tolerated with no reported adverse events, indicating a good safety profile for this antibiotic in the studied population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for small intestinal bacterial overgrowth in patients without irritable bowel syndrome. Boltin, D., Perets, TT., Shporn, E., et al.[2021]

Rifaximin has been shown to effectively eradicate small intestinal bacterial overgrowth (SIBO) in patients, as evidenced by decreased levels of hydrogen and methane in breath tests, with superior efficacy compared to other treatments in most studies.

In larger double-blind trials, including the TARGET 1 and TARGET 2 studies, rifaximin significantly improved global symptoms of irritable bowel syndrome (IBS) and bloating, although concerns about potential antimicrobial resistance were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin: The Revolutionary Antibiotic Approach for Irritable Bowel Syndrome. Triantafyllou, K., Sioulas, AD., Giamarellos-Bourboulis, EJ.[2019]

Rifaximin is effective in treating travelers' diarrhea caused by Escherichia coli, showing similar efficacy to ciprofloxacin, but it does not work against Campylobacter jejuni infections.

Beyond travelers' diarrhea, rifaximin has potential uses in treating various gastrointestinal disorders, including hepatic encephalopathy and Crohn's disease, due to its broad spectrum of activity and poor absorption in the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin: a nonabsorbed oral antibiotic. Baker, DE.[2018]

Approximately 41.67% of diarrhea-predominant irritable bowel syndrome (IBS-D) patients were found to have small intestinal bacterial overgrowth (SIBO), which can be effectively detected using a lactulose breath test that measures both hydrogen and methane levels.

Rifaximin treatment significantly improved symptoms such as abdominal pain and stool consistency in IBS-D patients with SIBO, and it also reduced hydrogen and methane levels in their breath, while showing limited effects on patients without SIBO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin]. Liu, ZJ., Wei, H., Duan, LP., et al.[2018]

Rifaximin significantly improved multiple symptoms of irritable bowel syndrome with diarrhea (IBS-D), including abdominal pain, bloating, and fecal urgency, in a study involving 1258 patients from double-blind trials and 2438 from an open-label trial.

Patients treated with rifaximin were more likely to achieve clinically relevant improvements in their symptoms as early as one week after treatment, with significant benefits maintained for at least five weeks, indicating its efficacy in managing IBS-D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin Treatment for Individual and Multiple Symptoms of Irritable Bowel Syndrome With Diarrhea: An Analysis Using New End Points. Lacy, BE., Chang, L., Rao, SSC., et al.[2023]

In a randomized double-blind placebo-controlled trial with 124 patients, rifaximin significantly improved symptoms of bloating and flatulence compared to placebo, with 41.3% of patients reporting relief versus 22.9% in the placebo group after treatment.

Rifaximin was found to be safe, with no reported adverse events, and its efficacy was particularly noted in patients with irritable bowel syndrome (IBS), where symptom improvement correlated with a significant reduction in H2-breath excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Sharara, AI., Aoun, E., Abdul-Baki, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3610260/

Rifaximin in irritable bowel syndrome: rationale, evidence ... Of the patients given rifaximin, 69% (58 out of 84) had a clinical response compared with only 38% (9 out of 24) of those on neomycin and 44% (27 out of 61) of ...

2. xifaxan.com xifaxan.com/hcp/ibsd/efficacy/

Efficacy Data for Adults with IBS-D In adults with IBS-D. 2 weeks of XIFAXAN provided significant relief of abdominal pain and diarrhea1,2,*. Percentage of composite efficacy responders in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10558962/

Effectiveness of Rifaximin on the Outcomes of Irritable ... The results of our meta-analysis support the use of rifaximin in the treatment of IBS, owing to its safety and effectiveness.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/021361s023lbl.pdf

XIFAXAN® (rifaximin) tablets, for oral use - accessdata.fda.gov In patients with irritable bowel syndrome with diarrhea (IBS-D) treated with XIFAXAN 550 mg three times a day for. 14 days, the median Tmax was 1 hour and mean ...

5. mayoclinic.org mayoclinic.org/drugs-supplements/rifaximin-oral-route/description/drg-20065817

Rifaximin (oral route) - Side effects & dosage Rifaximin is used to treat traveler's diarrhea that is caused by a bacteria called Escherichia coli. It is also used to prevent hepatic encephalopathy.

6. xifaxan.com xifaxan.com/hcp/ibsd/safety-and-dosing/

Safety Profile and Dosing for IBS-D | XIFAXAN® (rifaximin) Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK562329/

Rifaximin - StatPearls - NCBI Bookshelf For Irritable Bowel Syndrome with Diarrhea(IBS-D), the suggested dose of rifaximin is 400 mg three times or 550 mg twice daily for two weeks.

8. goodrx.com goodrx.com/xifaxan/what-is?srsltid=AfmBOoo4OzwSE8YLn8ktE4U1_EL_h23R-3tsOkCsJ-wu8E4wmWSnUFmD

Xifaxan (Rifaximin): Uses, Side Effects, Dosage & More Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology ...