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

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MetroHealth Medical Center; Ronnie Fass, MD
• Treatments: Rifaximin

Criteria

Inclusion Criteria:

1. Cirrhosis patients between 18-89 years 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.

Exclusion Criteria:

1. Known allergy to rifaximin / rifabutin / rifampin.

2. Use of antibiotics within last 6 weeks

3. Use of lactulose / lactitol, probiotics, L-ornithine- L -aspartate, zinc, metronidazole, or neomycin, within last 6 weeks

4. Use of any drug known to affect gastro-intestinal motility within the previous 2 to 4 weeks (such as, Reglan, Erythromycin, or Domeperidone)

5. Use of drugs such as opiates and antidepressants (except stable doses of selective serotonin re-uptake inhibitors)

6. 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

7. Diseases associated with poor gastrointestinal motility such as uncontrolled diabetes (A1c > 8%), rheumatological disorders (such as scleroderma and mixed connective tissue disorders [MCT])

8. History of gastrointestinal tract or abdominal surgery

9. Spontaneous peritonitis or other severe infections

10. Colonoscopy or enema treatment within 4 weeks

11. Hepatic encephalopathy with clinical signs

12. Inability to complete neuropsychiatric testing due to hearing loss, poor vision, etc.

13. Poorly compliant patients

14. 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.

15. Decompensated cirrhosis (i.e., history of variceal bleeding or ascites)

16. Total bilirubin = 2mg/dL or albumin < 3.5g/dL or international normalized ratio (INR) > 1.7

17. Patients with a calculated glomerular filtration rate (GFR) < 60mL/min/1.73m2

18. Patients with severe hepatic impairment (Child-Pugh score > 7)

19. Patients with untreated viral hepatitis

20. 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.

21. No concurrent use of P-glycoprotein inhibitors (e.g., cyclosporine)

22. Current abuse of alcohol or illicit drugs