Autonomic Dysfunction in Non-Alcoholic Fatty Liver Disease
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Neurology |
| Healthy: | No |
| Age Range: | 35 - 65 |
| Updated: | 8/3/2016 |
| Start Date: | May 2014 |
| End Date: | May 2016 |
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.
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.
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.
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.
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
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