Impact Of Choline in Patients With NAFLD

October 16, 2022 updated by: Amal A. Elkholy, Ain Shams University

The Impact Of Choline Administration On Oxidative Stress And Clinical Outcome Of Patients With Non-Alcoholic Fatty Liver Disease NAFLD

The study will be assessing the impact of choline supplementation in Non-alcoholic fatty liver disease patients using ultrasonography to show change in liver echogenicity, various laboratory tests as liver function, lipid profile and glucose control tests and finally on markers of oxidative stress as Thiobarbituric acid reactive substances and Leptin.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) has attracted increasing attention given its high prevalence, estimated at 20% to 44% in Western countries and 5% to 38% in Asia as well as its correlation with cardiovascular morbidity and mortality.

NAFLD is the result of hepatic fat accumulation in patients without a history of excessive alcohol consumption, predisposing medications or other defined liver disorders. NAFLD comprises a spectrum of liver disorders. At one end of this spectrum, is simple hepatic steatosis and the other end is non-alcoholic steatohepatitis (NASH) which is characterized by hepatocellular injury, inflammation and fibrosis sometimes leading to cirrhosis. It is considered the hepatic manifestation of metabolic syndrome, which is defined by the presence of central obesity, insulin resistance, hyperlipidemia, hyperglycemia, and hypertension.

According to the multiple parallel hits in NAFLD pathogenesis, the first hit is insulin resistance, which results in increased hepatic de novo lipogenesis and impaired adipose tissue lipolysis.These conditions cause an efflux of free fatty acids from the adipose tissue to the liver. The liver becomes vulnerable to a series of hits, including oxidative stress and dysregulation of adipokines such as leptin.

It has been also observed that fatty liver can occur both in people with a normal body mass index (BMI) (10-24% of the population has fatty liver) and in 95% of adults with obesity.

Choline is an essential nutrient for human health, which exerts various physiological functions:

  1. It is acetylated to generate acetylcholine, the important neurotransmitter;
  2. It is oxidized to pass methyl to S-adenosylmethionine, a universal methyl group donor, which participates in the methylation-dependent biosynthesis of DNA, RNA and protein;
  3. It is phosphorylated to synthesize phosphatidylcholine, a major constituent of cell and mitochondrial membranes, which is involved in the mitochondrial bioenergetics regulating lipid and glucose metabolism. In addition, it takes part in the packaging and exporting of triglyceride (TG) in very low-density lipoprotein (VLDL), as well as the solubilizing of bile salts for secretion.

Choline deficiency contributes to various disorders in animals and humans, with liver as its main target. Humans deprived of choline have been perceived to develop fatty liver, liver cell death or skeletal muscle damage, which were further proven by another clinical study revealing that patients fed with total parenteral nutrition (TPN) solutions low in choline resulted in TPN-associated liver disease.

Growing evidence has suggested certain effects of choline on mitochondrial metabolism. Low choline results in the altered composition of mitochondrial membranes, reduced mitochondrial membrane potential, decreased Adenosine triphosphate production and disturbance in fatty acid β-oxidation in rats fed a choline-deficient diet. This mitochondrial dysfunction has also been linked to the process of the increase of reactive oxygen species (ROS) generation, the loss of mitochondrial membrane potential, cellular apoptosis and hepatocarcinogenesis caused by choline deficiency in rat hepatocytes. However, the specific mechanisms connecting choline, DNA methylation and metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), remain to be evidently described.

Excessive energy substrates available to the hepatocytes can potentially result in cellular steatosis with the increasing generation of free fatty acids (FFA) and ROS, which, in turn, will lead to mitochondrial dysfunction inseparably linked with oxidative stress. This is fundamental to the development of dietary-induced NAFLD or TPN-associated liver disease under unbalanced nutrients distress and can potentially lead to steatohepatitis, fibrosis and cirrhosis in the liver.

Considering those mechanisms, hence it is interesting to study whether supplementation of choline could have a potential benefit in NAFLD patients. Choline has been shown to decrease lipoprotein oxidation, generation of inflammatory mediators and reactive oxygen species, maintain lipid and glucose homeostasis and help in the repair of mitochondrial membrane.

Patients with NAFLD exhibit increased levels of hepatic cytochrome P450-2E1 and thiobarbituric acid reactants, which are markers of lipid peroxidation. Oxidative stress has been demonstrated in animal and human studies to be a significant factor, responsible for causing progression of NAFLD to NASH. In this respect, it may be regarded as an important second hit.

Oxidative stress in fatty liver arises because of excessive fatty acid oxidation resulting in an increase release of reactive oxygen species. Another study demonstrated that, total lipid peroxidation products as represented by TBARS were significantly higher among patients with NAFLD as compared to patients with either chronic viral hepatitis or healthy controls.

This suggests that the occurrence of high plasma concentration of products of lipid peroxidation is a unique phenomenon in patients with NAFLD and not only a byproduct of any inflammation, because TBARS was lower among patients with chronic viral hepatitis who had high degree of necroinflammation.

Leptin, an important regulatory energy hormone, is released from adipocytes and may play a role in the development of liver steatosis. High levels of serum leptin have been reported in patients with NAFLD.

Although the underlying mechanisms of leptin in NAFLD are incompletely understood, it has been suggested that it affects fat deposition, fibrogenesis, and inflammation in the liver of patients with NAFLD.

In NAFLD, the dysregulation of adipokines, including leptin, mediate insulin resistance through reduced insulin signaling, increased fatty acid concentrations in the liver, and promote steatosis.In addition to hyperinsulinemia, a feature of insulin resistance is the stimulatory effect on the leptin gene, which causes the release of leptin in a vicious cycle.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult Patients from 18 to 65 years.
  2. Gender: both males and females (age and sex matched in both groups).
  3. Patients diagnosed with NAFLD via ultrasound (hepatic steatosis observation on ultrasound).
  4. Treatment free from choline supplementation for the past 3 months prior starting the therapeutic regimen.

Exclusion Criteria:

  1. Other liver diseases as viral hepatitis (B or C)
  2. Alcohol consumption more than 40 g per week for the past 12 months, and life-time cumulative consumption more than 100 kg.
  3. Autoimmune liver disease
  4. Malignancy of any nature.
  5. Any systemic failure (cardiovascular, renal or respiratory)
  6. Patients with major psychiatric illness.
  7. Pregnant or lactating women.
  8. Diabetes mellitus .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Choline supplement group
Phosphatidyl choline tablets at a dose of 1200 mg twice per day plus conventional management for 12 weeks
Dietary supplement: Phosphatidyl Choline
conventional management + phosphatidyl choline tablets
No Intervention: Control group
conventional management only for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
effect on Oxidative stress marker as the mean change of Thiobarbituric acid reactive substances level
Time Frame: 12 weeks
Measured as the mean change in Thiobarbituric acid reactive substances serum level (mmol/μg) at baseline and after 12 weeks of choline supplementation
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
effect on Inflammatory status as the mean change in leptin levels
Time Frame: 12 weeks
Measured by Inflammation marker as the mean change in serum leptin levels (ng/mL) at baseline and after 12 weeks of choline supplementation
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical outcome as measured by Hepatic ultrasonography
Time Frame: 12 weeks
ultrasonography measure the change in liver size at baseline and after 12 weeks.
12 weeks
Clinical outcome as measured by Hepatic US
Time Frame: 12 weeks
ultrasonography measure the change in echogenicity at baseline and after 12 weeks.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Investigators

  • Principal Investigator: Lamia El Wakeel, PhD, Ain Shams University
  • Principal Investigator: Doaa Zakaria, PhD, Ain Shams University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2022

Primary Completion (Anticipated)

November 1, 2023

Study Completion (Anticipated)

February 1, 2024

Study Registration Dates

First Submitted

November 17, 2021

First Submitted That Met QC Criteria

January 15, 2022

First Posted (Actual)

January 20, 2022

Study Record Updates

Last Update Posted (Actual)

October 18, 2022

Last Update Submitted That Met QC Criteria

October 16, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Choline in NAFLD

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-Alcoholic Fatty Liver Disease

Clinical Trials on Phosphatidyl Choline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe