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Rifaximin's Effect on Covert Hepatic Encephalopathy in Cirrhosis Patients With Small Intestinal Bacterial Overgrowth and Gastrointestinal Dysmotility

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ClinicalTrials.gov Identifier: NCT04244877
Recruitment Status : Not yet recruiting
First Posted : January 28, 2020
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Ronnie Fass, MD, MetroHealth Medical Center

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 three times daily for 2 weeks and then be treated with Rifaximin 550 mg PO twice daily for 6 more 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.

Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Minimal Hepatic Encephalopathy Small Intestinal Bacterial Overgrowth Gastrointestinal Motility Disorder Drug: Rifaximin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Therapeutic Effect of Rifaximin on Covert Hepatic Encephalopathy With Underlying Small Intestinal Bacterial Overgrowth and Gastrointestinal Dysmotility in Liver Cirrhosis Patients
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Rifaximin
Rifaximin 550 mg by mouth three time daily for two weeks followed immediately with Rifaximin 550 mg by mouth two times daily for six weeks.
Drug: Rifaximin
Drug: Rifaximin tablet
Other Name: Xifaxan




Primary Outcome Measures :
  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. [ Time Frame: 8 weeks ]
    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.


Secondary Outcome Measures :
  1. Improvement in small bowel motility in subjects taking Rifaximin [ Time Frame: 8 weeks ]
    The percent of patients with improvement in small bowel motility as measured by the SmartPill after taking Rifaximin for 8 weeks



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Cirrhosis patients between 18-70years of age, without prior transjugular intrahepatic portosystemic shunt (TIPS) placement or prior overt hepatic encephalopathy.
  2. Cirrhosis diagnosed on the basis of liver biopsy, liver stiffness measurement (Fibroscan) or radiological study.
  3. 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.
  4. No prior episode of overt HE, not on therapy for overt HE, not on any psycho-active medications apart from stable doses of selective serotonin re-uptake inhibitors.

Exclusion Criteria:

  1. Known allergy to rifaximin / rifabutin / rifampin.
  2. Current or recent (<6 months) abuse of alcohol or illicit drugs
  3. Use of antibiotics within last 6 weeks
  4. Use of lactulose / lactitol, probiotics, L-ornithine- L -aspartate, zinc, metronidazole, or neomycin, within last 6 weeks
  5. Use of any drug known to affect gastro-intestinal motility within the previous 2 to 4 weeks (such as, Reglan, erythromycin, or domperidone)
  6. Use of drugs such as opiates and antidepressants (except stable doses of selective serotonin re-uptake inhibitors)
  7. Diarrhea or abdominal distention
  8. Patients deemed higher risk for capsule retention including a history of esophageal stricture or Zenker's diverticulum, partial or complete bowel obstruction, known fistula, known large or numerous diverticula and dementia
  9. Diseases associated with poor gastrointestinal motility such as cardiac and pulmonary dysfunction, renal insufficiency, diabetes, rheumatological disorders (such as scleroderma and mixed connective tissue disorders)
  10. History of gastrointestinal tract or abdominal surgery
  11. Spontaneous peritonitis or other severe infections
  12. Colonoscopy or enema treatment within 4 weeks
  13. Hepatic encephalopathy with clinical signs
  14. Inability to complete neuropsychiatric testing due to hearing loss, poor vision, etc.
  15. Poorly compliant patients
  16. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04244877


Contacts
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Contact: Ronnie Fass, MD 216-778-3145 rfass@metrohealth.org
Contact: Sara Ghoneim, MD 2167770498 sghoneim@metrohealth.org

Sponsors and Collaborators
Ronnie Fass, MD
Investigators
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Principal Investigator: Ronnie Fass, MD Metrohealth Medical Center/Case Western Reserve University
Publications of Results:

Other Publications:

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Responsible Party: Ronnie Fass, MD, Director, Division of Gastroenterology and Hepatology, MetroHealth Medical Center
ClinicalTrials.gov Identifier: NCT04244877    
Other Study ID Numbers: IRB17-00550
First Posted: January 28, 2020    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Hepatic Encephalopathy
Brain Diseases
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Brain Diseases, Metabolic
Metabolic Diseases
Rifaximin
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents