Effect of Vitamin E on Non-Alcoholic Fatty Liver Disease

NCT02690792 | Completed

• 2 other identifiers: 102010-180R01DK087977-01A1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; NAFLD (Non-Alcoholic Fatty Liver Disease); NASH (Non-Alcoholic Steatohepatitis)

Keywords

Healthy; NAFLD; NASH; Liver Metabolism; Vitamin E

Outcome Measures

Primary Outcomes (3)

• Change in Measurement of percentage of Liver Fat by MRI

  Measurement of percentage of Liver Fat by MRI at baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks.

  baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks

• Change in Measurement of Insulin Sensitivity via Hyperinsulinemic glucose clamp

  Measurement of insulin sensitivity by glucose disposal rate (mg/Kg/min) via hyperinsulinemic glucose clamp @ baseline and 16 weeks.

  4 months

• Change in Measurement of glucose metabolism turnover by non-radioactive isotopic infusion and recovery

  Measurement of glucose metabolism turnover (ug/Kg/min) in the liver by non-radioactive isotopic infusion and recovery @ baseline and 16 weeks.

  4 months

Study Arms (2)

NAFLD/NASH - Placebo

PLACEBO COMPARATOR

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

NAFLD/NASH - Vitamin E

ACTIVE COMPARATOR

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

Interventions

NAFLD/NASH - Placebo OTHER

Placebo capsules, 2 capsules by mouth each morning and 2 capsules by mouth each evening for 4 months.

NAFLD/NASH - Placebo

NAFLD/NASH - Vitamin E DIETARY_SUPPLEMENT

Vitamin E 200 IU capsule, 2 capsules by mouth each morning and 2 capsules by mouth each evening for 4 months.

NAFLD/NASH - Vitamin E

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jeffrey Browning: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8568, United States

Location

Related Publications (1)

• Fu X, Fletcher JA, Deja S, Inigo-Vollmer M, Burgess SC, Browning JD. Persistent fasting lipogenesis links impaired ketogenesis with citrate synthesis in humans with nonalcoholic fatty liver. J Clin Invest. 2023 May 1;133(9):e167442. doi: 10.1172/JCI167442.

  PMID: 36928190 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Jeffrey D Browning, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: February 24, 2016
• Study Start: December 1, 2009
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 16, 2018

Record last verified: 2018-11

Locations

US (1)