Clinical trial NCT02132780: Autonomic Dysfunction in Non-Alcoholic Fatty Liver Disease
Official title: The Impact of Autonomic Dysfunction on Liver-Related Symptoms in Non-Alcoholic Fatty Liver Disease and Their Relationship to Systemic Inflammation and Insulin Resistance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-alcoholic Fatty Liver Disease
NAFLD
Fatty Liver, Nonalcoholic
Nonalcoholic Fatty Liver Disease
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2014-05-07
Enrollment: 25
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Adults with NAFLD who are patients at the NAFLD Clinic at VCU Health Systems in Richmond, VA.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Autonomic Dysfunction
timeFrame: baseline
Secondary outcomes:
measure: Relationship between AD and symptoms
timeFrame: baseline
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
Study officials:
affiliation: VCU
name: Kyungeh An, PhD
role: PRINCIPAL_INVESTIGATOR
References: