Autonomic Dysfunction in Non-Alcoholic Fatty Liver Disease (AD-NAFLD)

The Impact of Autonomic Dysfunction on Liver-Related Symptoms in Non-Alcoholic Fatty Liver Disease and Their Relationship to Systemic Inflammation and Insulin Resistance

There is a significant association between autonomic dysfunction and symptoms experienced by NAFLD patients mediated by increased systemic inflammation and insulin resistance, resulting in deteriorating quality of life of affected patients; fatigue and other symptoms drive worsening autonomic dysfunction in these patients. We aim to describe the severity of autonomic dysfunction (AD) in non-alcoholic fatty liver disease (NAFLD) and the relationship of AD to symptoms experienced by NAFLD patients (such as fatigue, chronic pain, depression, sleep disturbance, and cognitive dysfunction), and to the quality of life of NAFLD patients. We also hope to examine the impact of systemic inflammation and insulin resistance as mediators of manifestations of AD and symptoms experienced by NAFLD patients.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; NAFLD; Nonalcoholic Fatty Liver Disease; Fatty Liver, Nonalcoholic

Detailed Description

Aim 1. Describe the severity of AD in NAFLD and the relationship of AD to symptoms experienced by NAFLD patients (fatigue, chronic pain, depression, sleep disturbance, and cognitive dysfunction) (Aim 1a) and to the quality of life of NAFLD patients (Aim 1b). Primary screening for inclusion/exclusion criteria will be done at the VCUHS clinic. Subjects meeting inclusion criteria will be approached about study participation during their routine NAFLD clinic visit. Those who agree to participate in the study will return for a study visit at the CCTR Clinical Research Services. All subjects will be asked to fast and avoid caffeine for 12 hours prior to study visit. Demographic and clinical data will be collected by study coordinators. After a focused exam, conducted by a hepatologist to determine health status of the participants, the PI and a research nurse will interview participants to assess their symptoms and AD (Aim 1). Blood (20 ml) samples will be collected via venipuncture for serum and plasma inflammatory markers and IR (Aim 2).

Aim 2. Examine the impact of systemic inflammation (SI) and insulin resistance (IR) as mediators of manifestations of AD and symptoms experienced by NAFLD patients. Increased presence of adipocytes may produce high, chronic levels of cytokines such as IL-6 and TNF-α resulting in higher levels of APRPs which contribute to overall inflammation as well as cognitive decline and fatigue. Secondly, elevated levels of IL-6 and TNF-α lower levels of CTRPs which exacerbate IR, AD, and muscle and cardiac problems reported in NAFLD. Through the use of plasma analysis, levels of cytokines such as IL-6, TNF-α, and APRPs can be performed in a high throughput BioPlex® assay (Bio-Rad Laboratories, Inc.: Hercules, CA). We have extensive experience with these types of assays and have generated data using human samples in numerous studies conducted through the Center of Excellence for Biobehavioral Approaches to Symptom Management (CEBASM) at the School of Nursing. CTRP family members are also expressed in the plasma and at detectible levels. We will perform ELISA analysis to compare circulating levels of the various CTRPs using commercially available CTRP ELISA kits/reagents. Insulin resistance (IR) will be assessed by HOMO-IR utilizing fasting glucose and insulin.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults with NAFLD who are patients at the NAFLD Clinic at VCU Health Systems in Richmond, VA.

Description

Inclusion Criteria:

• Men and women within the age of 35-65
• understand and speak English
• NAFLD on liver histology by the biopsy within preceding 24 months

Exclusion Criteria:

• Patients with poorly controlled diabetes (HbA1c>8.5% or fasting blood glucose>150 mg/dl)
• renal dysfunction (Cr>1.5) last 3 months
• history of cardiac rhythm other than sinus rhythm
• on beta-blockers
• other liver diseases (HCV, HBV)
• decompensated cirrhosis (free of ascites hepatic encephalopathy, variceal bleeding)
• major depression
• cancer
• stroke
• any other major health conditions

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autonomic Dysfunction	Will record heart rate variability at the time of study visit and collect data from 24 hour automatic blood pressure readings. The Autonomic Symptoms Checklist will also be used.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between AD and symptoms	Data on symptoms will be collected using the Chronic Liver Disease Questionnaire and PROMIS symptom short forms for symptoms including fatigue, anxiety, sleep and depression. RBANS and Stroop will be used to assess cognitive function.	baseline

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Kyungeh An, PhD, VCU

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (Estimate): May 7, 2014

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: HM20000329; UL1TR000058 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We completed this pilot with 23 participants. Sharing data is to be determined.