Speech in Hepatic Encephalopathy (HE)

Analysis of Acoustic, Lexical, and Syntactic Speech Features in Hepatic Encephalopathy

This is an observational study that will test the clinical significance of speech features in patients with cirrhosis. It aims to assess if speech is associated with cognitive function at baseline, if speech predicts changes in cognition, and if speech predicts future events of hepatic encephalopathy (cirrhosis-related confusion), as well as to assess the dynamics of speech over time, especially with episodes of overt hepatic encephalopathy (OHE) and treatment interventions.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Behavioral: Home Recordings; Behavioral: In-patient Recordings; Behavioral: Same-Day Study Visit - Regular Appointment; Behavioral: Same-Day Study Visit - Procedure; Behavioral: Phone Call Follow-up Visits

• Study Type: Observational
• Enrollment (Actual): 251

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hepatology and Transplant Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study population consists of adult outpatients who are evaluated at the University of Michigan Hepatology Clinic.

Description

Inclusion Criteria for Patients with Cirrhosis:

• Cirrhosis, as diagnosed by imaging, elastography, biopsy, or decompensation
• Able to provide informed consent in English

Exclusion Criteria for Patients with Cirrhosis:

• Neurodegenerative disorder (other than hepatic encephalopathy) including Alzheimer's disease and dementia
• Prior stroke or Transischemic Attack (TIA)
• English not primary language for communication

Inclusion Criteria for Patients without Cirrhosis:

• Able to provide informed consent in English
• Fibroscan with stiffness <7 kPa

Exclusion Criteria for Patients without Cirrhosis:

• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >5 times the upper limit of normal in the last year
• History of cirrhosis by imaging or histology or clinical decompensation
• Neurodegenerative disorder (other than hepatic encephalopathy) including Alzheimer's disease and dementia
• Prior stroke or TIA

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Cirrhosis; This group will be composed of 200 patients with cirrhosis. Patients will be enrolled regardless of compensated vs. decompensated status, prior history of HE, Model for End Stage Liver Disease (MELD), and cirrhosis etiology.	Behavioral: Home Recordings; If patients are willing to download the Winterlight application to their personal iOS devices this will be done at study visit 1. The application will send a notification to the patient once per month, requesting that they perform a paragraph reading task, a picture description task, and an animal naming task.; Behavioral: In-patient Recordings; If patients are admitted to UM hospital for suspected or confirmed OHE, with patient assent, physician study staff will assist the patient in recording a paragraph reading task, a picture description task, and an animal naming task.; Behavioral: Same-Day Study Visit - Regular Appointment; Staff will call patients in anticipation of in-person regular visits to set up a same-day study visit. Patients will record the three speech tasks at this time.; Behavioral: Same-Day Study Visit - Procedure; Staff will call patients in anticipation of in-person procedure visits to set up a same-day study visit, prior to procedure if sedation is planned. Patients will record the three speech tasks at this time.; Behavioral: Phone Call Follow-up Visits; Non-physician study staff will call the patients every 3 months and, using a phone script, will ask them survey questions about their hepatic health.
Patients without Cirrhosis; This group will be composed of 50 patients without cirrhosis to act as controls. They will have been found on Fibroscan to not have significant fibrosis.	Behavioral: Home Recordings; If patients are willing to download the Winterlight application to their personal iOS devices this will be done at study visit 1. The application will send a notification to the patient once per month, requesting that they perform a paragraph reading task, a picture description task, and an animal naming task.; Behavioral: Same-Day Study Visit - Regular Appointment; Staff will call patients in anticipation of in-person regular visits to set up a same-day study visit. Patients will record the three speech tasks at this time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Psychometric Hepatic Encephalopathy Score (PHES) from Baseline to 6 Months	A well-validated pen-and-paper neurocognitive assessment tool to identify minimal Hepatic Encephalopathy (HE). Scores range from -15 to +5; values farther from 0 (normalized average) represent more significant deviation from the norm. Positive scores indicate better performance.	6 Months
Change in Psychometric Hepatic Encephalopathy Score (PHES) from Baseline to 12 Months	A well-validated pen-and-paper neurocognitive assessment tool to identify minimal Hepatic Encephalopathy (HE). Scores range from -15 to +5; values farther from 0 (normalized average) represent more significant deviation from the norm. Positive scores indicate better performance.	12 Months
Speech Assessments	Recorded speech tasks comprising 3 sections: paragraph reading test, picture description test, and animal naming test.	12 Months
Time to Overt Hepatic Encephalopathy (HE)	Patient-reported HE episodes and HE episodes resulting in patient admission to University of Michigan hospital. Information collected includes: Date of symptom onset, duration of HE episode, and changes to medications.	12 Months

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Winterlight Labs
• Investigators: Principal Investigator: Patricia Bloom, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Actual): July 24, 2024
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: May 14, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Nutritional and Metabolic Diseases; Hepatic Encephalopathy
• Other Study ID Numbers: HUM00191626

Drug and device information, study documents

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