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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication rifaximin can reduce bloating in individuals with diabetic gastroparesis, a condition where the stomach can't empty properly, causing symptoms like nausea and abdominal pain. Participants will receive either rifaximin (also known as Xifaxan, Zaxine, Ciboz, Xifapill, Alfa Normix, or Flonorm) or a placebo (a look-alike pill with no active ingredients) for comparison. This trial may suit individuals with diabetic gastroparesis who frequently experience bloating. Those who have had recent stomach surgery or use certain medications like opioids or cannabis cannot participate. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research shows that rifaximin is safe and generally well-tolerated. Studies have found that patients using rifaximin for long-term treatment did not experience any serious side effects. One study noted no deaths linked to its use during clinical trials. This antibiotic treats conditions like irritable bowel syndrome with diarrhea and lowers the risk of liver-related brain issues.

In trials for these conditions, rifaximin did not raise major safety concerns. Evidence suggests it is a relatively safe treatment option, with most patients handling it well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gastroparesis?

Rifaximin is unique because it targets gut bacteria, which is a different approach than most gastroparesis treatments that focus on stimulating stomach muscles or controlling symptoms like nausea. This antibiotic has an anti-inflammatory effect in the gut, which might help reduce symptoms linked to gastroparesis. Researchers are excited because Rifaximin could offer a new way to manage the condition, especially for those who don't respond well to existing medications.

What evidence suggests that rifaximin might be an effective treatment for gastroparesis?

Research has shown that rifaximin, which participants in this trial may receive, can help reduce bloating. One study found that people who took 1,650 mg of rifaximin daily experienced less bloating than those who took a placebo, a pill with no active medicine. Rifaximin is a special antibiotic that works in the gut and doesn't absorb into the rest of the body, making it safer for long-term use. It has also helped with other gut issues, supporting its potential to ease symptoms of gastroparesis, such as bloating. ^{5 6 7 8 9}

Who Is on the Research Team?

Brian E Lacy

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4737517/

Rifaximin: A Unique Gastrointestinal-Selective Antibiotic for ... In a large randomized, double-blind, placebo-controlled trial (n=299), rifaximin at a dose of 1100 mg per day reduced the risk of developing breakthrough PSE by ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4970477/

Use of rifaximin in gastrointestinal and liver diseases - PMC CONCLUSION. Rifaximin is a broad spectrum poorly absorbed oral antibiotic with proven efficacy in a number of gastrointestinal and liver conditions (Table 1).

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163445304001197

Rifaximin—a novel antimicrobial for enteric infections Rifaximin shortens the duration of travelers' diarrhea and non-dysenteric diarrheal illness due to enterotoxigenic, enteroaggregative E. coli and Shigella ...

4. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.696065/full

Efficacy and Safety of Rifaximin Versus Placebo or Other ... The pooled data revealed that rifaximin significantly reduced the risk of a breakthrough episode compared with the controls (RR = 1.33, 95% CI = ...

5. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/rifaximin-decreases-bloating-in-patients-with-gastrointestinal-disorders/

Rifaximin Decreases Bloating in Patients With ... Treatment with rifaximin 1,650 mg per day showed significant improvement in bloating severity, compared with placebo (pooled SMD, -0.27; 95% CI, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24365449/

Rifaximin is safe and well tolerated for long-term maintenance ... Results: In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure.

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

Rifaximin - StatPearls - NCBI Bookshelf Rifaximin is an antibiotic used to treat irritable bowel syndrome with diarrhea, reduce the risk of overt hepatic encephalopathy recurrence in adults, and ...

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

XIFAXAN® (rifaximin) tablets, for oral use - accessdata.fda.gov The safety of XIFAXAN for the treatment of IBS-D was evaluated in 3 placebo-controlled studies in which 952 patients were randomized to XIFAXAN 550 mg three ...

9. en.wikipedia.org en.wikipedia.org/wiki/Rifaximin

Rifaximin Clinical trials did not show any serious adverse events while using rifaximin. There were no deaths while using it in the clinical trials.