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Effect of Vitamin E on Non-Alcoholic Fatty Liver Disease

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ClinicalTrials.gov Identifier: NCT02690792
Recruitment Status : Completed
First Posted : February 24, 2016
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Jeffrey Browning, University of Texas Southwestern Medical Center

Brief Summary:

One-third of the US population has non-alcoholic fatty liver disease (NAFLD) due to obesity and ~8 million of these individuals have a progressive form of the disease, non-alcoholic steatohepatitis (NASH). Currently, there are no noninvasive ways to determine which individuals with NAFLD will develop NASH. This is of medical importance since NASH can be a prelude to the development of end-stage liver disease.

The study of NAFLD has been limited by several factors, including the difficulties associated with studying liver metabolism in vivo in humans. Our group has pioneered new methods that use nuclear magnetic resonance (NMR) to measure intermediary hepatic metabolism in humans with a goal of directly studying the pathophysiology of bland steatosis and NASH. In this study, these noninvasive methods will be used to characterize and compare the metabolic alterations that accompany bland steatosis and NASH and test the hypothesis that detects if hepatic mitochondrial metabolism contribute to both disorders. Such characterization is fundamental to establishing a rational approach to the prevention and treatment of NAFLD and may provide simple, non-invasive methods to differentiate benign and progressive forms of NAFLD.

This proposal will be addressed via separate isotopic studies occurring at different time points during a prolonged fast. In subjects with NAFLD, these studies will be carried out before and after treatment with Vitamin E or placebo.

Healthy subjects will participate in initial baseline studies only without Vitamin E or placebo intervention.

The study is designed to harness the physiologic changes that occur with short- and long-term fasting to provide a rapid and cost-effective method to accomplish the aims of the application.


Condition or disease Intervention/treatment Phase
Healthy NAFLD (Non-Alcoholic Fatty Liver Disease) NASH (Non-Alcoholic Steatohepatitis) Other: NAFLD/NASH - Placebo Dietary Supplement: NAFLD/NASH - Vitamin E Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Role of Mitochondrial Dysfunction in Non-Alcoholic Fatty Liver Disease
Actual Study Start Date : December 2009
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Placebo Comparator: NAFLD/NASH - Placebo

In NAFLD/NASH Group: Identically appearing Placebo capsules given as double-blinded, randomized intervention as a comparator to Vitamin E intervention.

Dosage: Placebo capsules. Two capsules by mouth each morning and two capsules by mouth each evening for 4 months.

Other: NAFLD/NASH - Placebo
Placebo capsules, 2 capsules by mouth each morning and 2 capsules by mouth each evening for 4 months.

Active Comparator: NAFLD/NASH - Vitamin E

In NAFLD/NASH Group: Vitamin E capsules given as double-blinded, randomized intervention as a comparator to Placebo capsules intervention.

Dosage: Vitamin E 200 IU/capsule. Two capsules by mouth each morning and two capsules by mouth each evening for 4 months.

Dietary Supplement: NAFLD/NASH - Vitamin E
Vitamin E 200 IU capsule, 2 capsules by mouth each morning and 2 capsules by mouth each evening for 4 months.




Primary Outcome Measures :
  1. Change in Measurement of percentage of Liver Fat by MRI [ Time Frame: baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks ]
    Measurement of percentage of Liver Fat by MRI at baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks.

  2. Change in Measurement of Insulin Sensitivity via Hyperinsulinemic glucose clamp [ Time Frame: 4 months ]
    Measurement of insulin sensitivity by glucose disposal rate (mg/Kg/min) via hyperinsulinemic glucose clamp @ baseline and 16 weeks.

  3. Change in Measurement of glucose metabolism turnover by non-radioactive isotopic infusion and recovery [ Time Frame: 4 months ]
    Measurement of glucose metabolism turnover (ug/Kg/min) in the liver by non-radioactive isotopic infusion and recovery @ baseline and 16 weeks.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

NAFLD/NASH SUBJECTS

  • Male and Female, Age 18-65 years of all racial and ethnic origins
  • Hepatic steatosis by radiologic study with or without liver enzyme elevation
  • BMI < 35 kg/m2
  • English or Spanish language
  • Females of childbearing potential must be willing to practice an acceptable form of birth control throughout the protocol
  • May also have Type 2 Diabetes (T2DM) with:

Hemoglobin A1C < 8.5 % of total Prior, current or no oral antidiabetic medication usage

CONTROL SUBJECTS:

  • Age 18-65 years.
  • BMI ≤ 35 kg/m2
  • English or Spanish language
  • Females of childbearing potential must be willing to practice an acceptable form of birth control throughout the protocol
  • May also have T2DM with:

Hemoglobin A1C < 8.5 % of total Prior, current or no oral antidiabetic medication usage

Exclusion Criteria:

ALL SUBJECTS:

  • Diabetes type 1
  • Diabetes type 2 with:

Hemoglobin A1C < 8.5 % of total Current or prior insulin usage

  • Medications or conditions that confound the diagnosis of NAFLD
  • Excessive alcohol intake (>30 g/day in men and >20 g/day in women)
  • Chronic liver disease other than NAFLD/NASH
  • Glucocorticoids
  • Medications or conditions that alter hepatic metabolism
  • Autoimmune disorders
  • Current or chronic infection
  • Other endocrine disorders
  • Recent weight loss (> 10 lbs. within the past 3 months)
  • Prescription weight-loss medications
  • Medical conditions likely to increase the risk of intervention Renal insufficiency (creatinine > 1.4 mg/dL) Baseline metabolic acidosis Congestive heart failure
  • Conditions or behaviors likely to affect the conduct of the study Pregnancy and breastfeeding confirmed by urine pregnancy test prior to all imaging or invasive procedure such as the euglycemic clamp, stable isotope studies, as well as prior to initiation of Vitamin E.
  • Concurrent participation in another research project
  • Inability to accept treatment assignment
  • Major psychiatric disorder or substance abuse

CONTROL SUBJECTS (in addition to the above):

  • Liver disease Elevated liver function tests Hepatic steatosis
  • Metabolic syndrome Hypertriglyceridemia (fasting plasma triglycerides > 150 mg/dL). Systolic blood pressure > 140 mmHg Diastolic blood pressure > 80 mmHg
  • Exercise above activities of daily living

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02690792


Locations
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United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-8568
Sponsors and Collaborators
Jeffrey Browning
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Jeffrey D Browning, M.D. University of Texas Southwestern Medical Center

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Responsible Party: Jeffrey Browning, Associate Professor of Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02690792     History of Changes
Other Study ID Numbers: 102010-180
R01DK087977-01A1 ( U.S. NIH Grant/Contract )
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: November 16, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Jeffrey Browning, University of Texas Southwestern Medical Center:
Healthy
NAFLD
NASH
Liver Metabolism
Vitamin E

Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents