Rifaximin's Effect on Covert Hepatic Encephalopathy With SIBO and Gastrointestinal Dysmotility

NCT04244877 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: IRB17-00550
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Small Intestinal Bacterial Overgrowth (SIBO) is a common and increasingly recognized disorder in cirrhosis (30% to 73%). One of the most important predisposing factors of SIBO is small bowel dysmotility. Multiple studies have shown that the presence of SIBO is strongly linked to the pathogenesis of Minimal Hepatic Encephalopathy (MHE) also known as Covert Hepatic Encephalopathy (CHE). Consequently, altering and modulating the intestinal microbiota with ammonia-lowering agents and Rifaximin has been the target treatment strategy in CHE. The aim of this study is to determine the therapeutic effect of Rifaximin on patients with CHE and underlying SIBO while assessing the influence of Rifaximin on small bowel motility. In this prospective interventional study, 40 patients with liver cirrhosis will be screened for Covert Hepatic Encephalopathy (CHE) using neuro-psychometric tests. Patients diagnosed with CHE will undergo breath test (BT) for SIBO screening. Afterwards, wireless motility capsule (The SmartPill) will be performed in all patients with a positive BT. Thereafter, the cirrhotic patients diagnosed with CHE and SIBO will receive Rifaximin 550 mg PO twice daily for eight weeks. At the end of treatment, neuro-psychometric tests will be repeated to evaluate the therapeutic effect on CHE. In addition, BT and SmartPill will be repeated at the completion of the Rifaximin treatment period to assess the effect on small bowel motility. All collected clinical parameters at the end of the study will be compared to baseline values.

Conditions

Cirrhosis, Liver; Minimal Hepatic Encephalopathy; Small Intestinal Bacterial Overgrowth; Gastrointestinal Motility Disorder

Outcome Measures

Primary Outcomes (1)

• Comparing the effects of Rifaximin on patients with covert hepatic encephalopathy (CHE) and SIBO using neuropsychometric test (NST) and glucose hydrogen breath test (BT) after 8 weeks of Rifaximin.

  The percent of subjects with improvement on Portosystemic Encephalopathy Syndrome test (PSE) after taking Rifaximin for 8 weeks. The percent of subjects who test negative on glucose breath test (BT) after treatment with Rifaximin.

  8 weeks

Secondary Outcomes (1)

• Improvement in small bowel motility in subjects taking Rifaximin

  8 weeks

Study Arms (1)

Rifaximin

EXPERIMENTAL

Rifaximin 550 mg by mouth twice daily for eight weeks.

Drug: Rifaximin

Interventions

Rifaximin DRUG

Drug: Rifaximin tablet

Also known as: Xifaxan

Rifaximin

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cirrhosis patients between 18-89 years of age, without prior transjugular intrahepatic portosystemic shunt (TIPS) placement or prior overt hepatic encephalopathy.
• Cirrhosis diagnosed on the basis of liver biopsy, liver stiffness measurement (Fibroscan) or radiological study.
• CHE diagnosis using pre-defined criteria \[two of the following should be abnormal as compared to healthy controls: number connection test A/B (NCT-A/B), Digit Symbol Test (DST), or Block Design Test (BDT)\] at least 2 months prior to the start of the study (beyond 2 standard deviation of normal). Testing will be carried out by a trained psychologist.

You may not qualify if:

• Known allergy to rifaximin / rifabutin / rifampin.
• Use of antibiotics within last 6 weeks
• Use of lactulose / lactitol, probiotics, L-ornithine- L -aspartate, zinc, metronidazole, or neomycin, within last 6 weeks
• Use of any drug known to affect gastro-intestinal motility within the previous 2 to 4 weeks (such as, Reglan, Erythromycin, or Domeperidone)
• Use of drugs such as opiates and antidepressants (except stable doses of selective serotonin re-uptake inhibitors)
• Patients deemed higher risk for capsule retention including a history of esophageal stricture or Zenker's diverticulum, partial or complete bowel obstruction, known fistulas, known large or numerous diverticula and dementia
• Diseases associated with poor gastrointestinal motility such as uncontrolled diabetes (A1c \> 8%), rheumatological disorders (such as scleroderma and mixed connective tissue disorders \[MCT\])
• History of gastrointestinal tract or abdominal surgery
• Spontaneous peritonitis or other severe infections
• Colonoscopy or enema treatment within 4 weeks
• Hepatic encephalopathy with clinical signs
• Inability to complete neuropsychiatric testing due to hearing loss, poor vision, etc.
• Poorly compliant patients
• Rifaximin - Pregnancy Category C- There are no adequate and well controlled studies in pregnant women. Rifaximin has been shown to be teratogenic in rats and rabbits at doses that caused maternal toxicity. Female study subjects of childbearing potential must have a negative pregnancy test and agree to use an acceptable method of contraception throughout the study. Participants that are breastfeeding are excluded.
• Decompensated cirrhosis (i.e., history of variceal bleeding or ascites)

Sponsors & Collaborators

• MetroHealth Medical Center: lead

Related Publications (19)

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  PMID: 19302262 RESULT

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  PMID: 26644276 RESULT

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Ronnie Fass, MD

  Metrohealth Medical Center/Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Gastroenterology and Hepatology

Study Record Dates

• First Submitted: December 27, 2019
• First Posted: January 28, 2020
• Study Start: September 15, 2021
• Primary Completion: May 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share