Rifaximin for Gastroparesis

Overseen By Kristen Lozano

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opioids, Cannabis, Antibiotics, Antifungals

Disqualifiers: Stomach surgery, GI obstruction, others

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: 2

Duration: 8 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you have used opioids, cannabis, antibiotics, or antifungal agents in the past 4 weeks.

Is Rifaximin safe for human use?

Rifaximin is generally considered safe for human use, with studies showing it is poorly absorbed in the body, which limits side effects. In trials, any adverse events were not serious and not related to the medication. ^{1 2 3 4 5}

How does the drug Rifaximin differ from other treatments for gastroparesis?

Rifaximin is unique because it is an antibiotic that targets gut bacteria, which may help reduce symptoms of gastroparesis by altering the gut microbiome, unlike other treatments that primarily focus on enhancing stomach motility. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing whether rifaximin can help people with diabetic gastroparesis who have bloating. Rifaximin is an antibiotic that reduces bacteria in the gut. By lowering these bacteria, it may help reduce bloating symptoms.

Research Team

Brian E Lacy

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults aged 18-75 with diabetic gastroparesis, previously diagnosed by symptoms and delayed gastric emptying, can join this trial. Excluded are those with prior stomach surgery, GI obstruction, recent opioid or antibiotic use, untreated severe anxiety or depression, active cannabis use, recent antifungal treatment, rifaximin treatment within the last year or uncontrolled diabetes (HgbA1c > 12).

Inclusion Criteria

I have been diagnosed with diabetic gastroparesis based on specific symptoms and tests.

Exclusion Criteria

I have not used antifungal agents in the last 4 weeks.

I have taken antibiotics within the last 4 weeks.

You are currently using cannabis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rifaximin or placebo for diabetic gastroparesis

8 weeks

Visits at week 2, week 4, and week 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Rifaximin

Trial Overview The study is testing if rifaximin improves bloating in patients with diabetic gastroparesis compared to a placebo. Participants will be randomly assigned to receive either the medication or an inactive substance.

Participant Groups

Group I: Intervention Treatment Experimental Treatment 1 Intervention

Subjects diagnosed with gastroparesis will receive Rifaximin

Group II: Placebo Group Placebo Group 1 Intervention

Subjects diagnosed with gastroparesis will receive a placebo

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

Rifaximin is a minimally absorbed antibiotic that effectively treats traveler's diarrhea caused by noninvasive bacteria, with a high fecal concentration of the drug (8000 microg/g) after just 3 days of therapy, leading to minimal systemic side effects.

Unlike its related drug rifampin, rifaximin has not shown a tendency to cause resistant bacterial strains, making it a safer option for treating gastrointestinal disorders, with potential applications beyond diarrhea, such as in hepatic encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Adachi, JA., DuPont, HL.[2022]

In a study involving 43 patients with liver cirrhosis, both low-dose (800 mg/day) and high-dose (1200 mg/day) rifaximin significantly reduced serum endotoxin levels after 2 weeks, indicating effective management of endotoxemia.

The effects of high-dose rifaximin persisted for at least 4 weeks after treatment cessation, and the safety profile was similar across all groups, suggesting that lower doses may be just as effective without increasing risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study. Zeng, X., Tang, XJ., Sheng, X., et al.[2018]

In a randomized controlled study involving 143 patients, rifaximin was found to be as effective as ciprofloxacin for treating acute infectious diarrhea, with no significant differences in the time to last unformed stool or overall wellness.

Both medications had similar safety profiles, with no significant differences in adverse events, suggesting that rifaximin is a viable alternative to ciprofloxacin, especially in light of increasing resistance to the latter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of rifaximin compared with ciprofloxacin for the treatment of acute infectious diarrhea: a randomized controlled multicenter study. Hong, KS., Kim, YS., Han, DS., et al.[2021]

A study involving 24 healthy volunteers found that the generic formulation of rifaximin had significantly higher systemic bioavailability compared to the branded rifaximin-α, with increases in key pharmacokinetic parameters like Cmax and AUC ranging from 165% to 345%.

The differences in absorption between the generic and branded formulations suggest that therapeutic outcomes may vary, and results from studies on rifaximin-α should not be directly applied to generic rifaximin due to these significant differences in systemic absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers. Blandizzi, C., Viscomi, GC., Marzo, A., et al.[2018]

In a study involving 10 patients with diabetes and moderate-to-severe gastroparesis, TZP-101 significantly improved gastric emptying times, reducing solid meal half-emptying by 20% and latency times by 34% compared to placebo.

TZP-101 was well-tolerated with mostly mild and self-limiting adverse events, indicating a favorable safety profile for this ghrelin agonist in treating gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Ejskjaer, N., Vestergaard, ET., Hellström, PM., et al.[2012]

In a study of 16 patients with idiopathic gastroparesis, ranitidine was found to induce gastroduodenal phase 3 activity in 87.5% of patients, significantly more than neostigmine, which only had this effect in 25% of patients.

The ability of ranitidine to trigger this motor activity is not due to its weak cholinergic properties, suggesting that it may work through an unknown mechanism that activates the neurohormonal program responsible for the migrating motor complex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between the effects of neostigmine and ranitidine on interdigestive gastroduodenal motility of patients with gastroparesis. Bortolotti, M., Cucchiara, S., Sarti, P., et al.[2018]

In a phase II trial involving 80 participants, revexepride, a 5-HT4 receptor agonist, did not show significant improvement in gastrointestinal symptoms or gastric emptying rates compared to placebo after 4 weeks of treatment.

Despite the lack of efficacy, revexepride was found to be generally safe and well-tolerated by participants, indicating it may not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial: a controlled pilot trial of the 5-HT4 receptor agonist revexepride in patients with symptoms suggestive of gastroparesis. Tack, J., Rotondo, A., Meulemans, A., et al.[2017]

A patient with gastroparesis experienced complete remission of symptoms like nausea and vomiting within one week of starting mirtazapine after failing to respond to multiple conventional treatments over seven months.

This case suggests that mirtazapine could be a promising alternative treatment for patients with gastroparesis who do not respond to standard prokinetic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Kim, SW., Shin, IS., Kim, JM., et al.[2018]

Ranitidine and itopride, when tested on isolated rabbit duodenum, showed a significant synergistic effect in promoting contractions at low doses, indicating their potential combined use for treating conditions like gastroparesis and GERD.

While ranitidine enhanced the prokinetic effect of itopride at lower concentrations, this effect diminished at higher doses, suggesting that careful dosing is important for maximizing therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study. Butt, AI., Khan, BT., Khan, A., et al.[2018]

References

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

Rifaximin: a nonabsorbed oral antibiotic. [2018]

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

Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study. [2018]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of rifaximin compared with ciprofloxacin for the treatment of acute infectious diarrhea: a randomized controlled multicenter study. [2021]

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

Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers. [2018]

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

Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. [2012]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison between the effects of neostigmine and ranitidine on interdigestive gastroduodenal motility of patients with gastroparesis. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Randomized clinical trial: a controlled pilot trial of the 5-HT4 receptor agonist revexepride in patients with symptoms suggestive of gastroparesis. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. [2018]

10. Pakistan pubmed.ncbi.nlm.nih.gov

Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study. [2018]