Transcranial Doppler Ultrasound and Minimal Hepatic Encephalopathy

Minimal Hepatic Encephalopathy is Associated With Increased Cerebral Vascular Resistance. a Transcranial Doppler Ultrasound Study

Minimal hepatic encephalopathy (MHE) is a subclinical complication of liver cirrhosis with a relevant social impact. Thus, there is urgent need to implement easy to use diagnostic tools for the early identification of affected patients.

This study was aimed to investigate cerebral blood flow, systemic hemodynamics as well as endothelial function of cirrhotic patients with MHE, and to verify their change after treatment with rifaximin.

Study Overview

• Status: Completed
• Conditions: Minimal Hepatic Encephalopathy
• Intervention / Treatment: Drug: Rifaximin

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Agostino Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All cirrhotic patients evaluated at the Department of Internal Medicine, Gastroenterology and Hepatology of the Fondazione Policlinico A. Gemelli in Rome

Description

Inclusion Criteria:

• diagnosis of liver cirrhosis on the basis of clinical, laboratory and ultrasound findings

Exclusion Criteria:

• active alcohol abuse (excessive alcohol intake stopped more than 6 months before the enrollment);
• chronic pulmonary diseases; ongoing infections; cerebrovascular diseases; primary or secondary cerebral neoplasm; primary liver neoplasm; heart function failure; chronic kidney disease; peripheral vascular disease; treatment with rifaximin or systemic antibiotics in the previous 15 days;
• smoking habit;
• grade 1 or overt hepatic encephalopathy.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cirrhosis no MHE; Patients with liver cirrhosis without signs of minimal hepatic encephalopathy
Cirrhosis MHE; Patients with liver cirrhosis with minimal hepatic encephalopathy	Drug: Rifaximin; to investigate changes in cerebral, splanchnic hemodynamics and endothelial function in cirrhotic patients with MHE after 15 days of rifaximin therapy (1200 mg/d)
Controls; Healhty subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of middle cerebral artery resistive index	Quantification of middle cerebral artery resistive index by Doppler ultrasound in patients with liver cirrhosis with or without MHE	baseline
Quantification of middle cerebral artery pulsatility index	Quantification of middle cerebral artery pulsatility index by Doppler ultrasound in patients with liver cirrhosis with or without MHE	baseline
Quantification of posterior cerebral artery resistive index	Quantification of posterior cerebral artery resistive index by Doppler ultrasound in patients with liver cirrhosis with or without MHE	baseline
Quantification of posterior cerebral artery pulsatility index	Quantification of posterior cerebral artery pulsatility index by Doppler ultrasound in patients with liver cirrhosis with or without MHE	baseline
Change in middle cerebral artery resistive index after treatment with rifaximin	Variation of middle cerebral artery resistive index measured by Doppler ultrasound after treatment with rifaximin 1200 mg/d for 15 days in patients with liver cirrhosis and MHE	at the end of rifaximin treatment (15 days)
Change in middle cerebral artery pulsatility index after treatment with rifaximin	Variation of middle cerebral artery pulsatility index measured by Doppler ultrasound after treatment with rifaximin 1200 mg/d for 15 days in patients with liver cirrhosis and MHE	at the end of rifaximin treatment (15 days)
Change in posterior cerebral artery resistive index after treatment with rifaximin	Variation of posterior cerebral artery resistive index measured by Doppler ultrasound after treatment with rifaximin 1200 mg/d for 15 days in patients with liver cirrhosis and MHE	at the end of rifaximin treatment (15 days)
Change in posterior cerebral artery pulsatility index after treatment with rifaximin	Variation of posterior cerebral artery pulsatility index measured by Doppler ultrasound after treatment with rifaximin 1200 mg/d for 15 days in patients with liver cirrhosis and MHE	at the end of rifaximin treatment (15 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of renal artery resistive index of cirrhotic patients with MHE compared to those without	Comparison of renal artery resistive index measured by Doppler ultrasound of cirrhotic patients with MHE and those without	baseline
Comparison of splenic artery resistive index of cirrhotic patients with MHE compared to those without	Comparison of splenic artery resistive index measured by Doppler ultrasound of cirrhotic patients with MHE and those without	baseline
Comparison of flow mediated dilation of cirrhotic patients with MHE compared to those without	Comparison of endothelial function (flow mediated dilation measured by Doppler ultrasound) of cirrhotic patients with MHE and those without	baseline
Change in renal artery resistive index after treatment with rifaximin	Change in renal artery resistive index measured by Doppler ultrasound in patients with liver cirrhosis and MHE after treatment with rifaximin 1200 mg/d for 15 days	at the end of rifaximin treatment (15 days)
Change in splenic artery resistive index after treatment with rifaximin	Change in splenic artery resistive index measured by Doppler ultrasound in patients with liver cirrhosis and MHE after treatment with rifaximin 1200 mg/d for 15 days	at the end of rifaximin treatment (15 days)
Change in flow mediated dilation after treatment with rifaximin	Change in endothelial function (flow mediated dilation measured by Doppler ultrasound) in patients with liver cirrhosis and MHE after treatment with rifaximin 1200 mg/d for 15 days	at the end of rifaximin treatment (15 days)

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 30, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: 1712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No