Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions

The purpose of this study is to evaluate the effect of a one-year nutritional intervention with either betaine or vitamin E supplementation, or a weight reducing diet and exercise program on liver steatosis and steatohepatitis.

Study Overview

• Status: Terminated
• Conditions: HIV Infections; Fatty Liver
• Intervention / Treatment: Drug: antioxidant vitamin E; Behavioral: weight reduction and exercise

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network, Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Baseline liver biopsy with macrovesicular fatty degeneration with inflammation (lobular or portal), with or without Mallory bodies, hepatocyte damage, and/or fibrosis diagnostic of NAFLD
• Convincing evidence of negligible alcohol consumption (< 20 grams of ethanol per day) obtained from a detailed history, confirmed by at least one close relative
• If hyperlipidemia or diabetes, stable drug regimen required for the 6 months prior to and during the study
• Willingness to maintain stable weight and normal exercise program for the duration of the study, if randomized to vitamin E or betaine

Exclusion Criteria:

• Liver disease of other etiology diagnosed as per routine medical investigation (e.g., chronic viral hepatitis, auto-immune chronic hepatitis, primary biliary cirrhosis or genetic liver disease such as Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, or biliary obstruction)
• Complications of liver disease such as recurrent variceal bleeding, resistant ascites, spontaneous portosystemic encephalopathy, or bacterial peritonitis
• Concurrent medical illness contra-indicating a liver biopsy, history of unexplained bleeding, hemophilia or abnormal coagulation results as per routine laboratory work-up or other reason judged by the hepatologist to contra-indicate a percutaneous liver biopsy
• Medications known to precipitate steatohepatitis (corticosteroids, high dose estrogens, methotrexate, amiodarone, calcium channel blockers, spironolactone, sulfasalazine, naproxen, oxacillin or ampinovire) in the 6 months prior to entry
• Antioxidant vitamin supplementation, ursodeoxycholic acid, or any other experimental drug 6 months prior to study entry
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vitamin E; alpha-tocoperol, capsules, 2 per day

Drug: antioxidant vitamin E; Vitamin E 800IU per day for 12 months; Behavioral: weight reduction and exercise; Patients will be asked to consume a self-selected, low fat, low-calorie diet of approximately 1200 kcal/d, which is consistent with American Heart Association guidelines for healthy weight reduction. Subjects will be provided with a videotape involving a structured 20 min aerobic exercise to be performed 3x/week.; Other Names: This arm was removed from the study protocol, as the enrollment was slow and; a high drop-out rate was observed in the weigh-loss arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change in grading of inflammation assessed by liver biopsy from month 0 to month 12 of the study	month 0 and month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver histology for steatosis and fibrosis staging		month 0 and month 12
Liver immuno-histochemistry for adducts of MDA: a product of LP		month 0 and month 12
Alpha-smooth muscle actin (alpha-SMA): a marker of hepatic stellate cell activation		month 0 and month 12
Transforming growth factor (TGF-beta): a pro-fibrogenic cytokine involved in fibrogenesis		month 0 and month 12
Liver lipid peroxides and TNP-alpha	For oxidative stress and inflammation in the liver	month 0, month 6 and month 12
Liver steatosis and volume will be assessed by ultrasound		month 0 and month 12
Liver enzymes and IR (HOMA and QUICKY) will also be measured		month 0, month 6 and month 12
Lipid peroxides, TNF-alpha, vitamin E and C in plasma	Parameters for oxidative stress and antioxidant capacity	month 0, month 6 and month 12

Collaborators and Investigators

• Sponsor: Johane Allard
• Collaborators: Ontario HIV Treatment Network
• Investigators: Principal Investigator: Allard Johane, MD, FRCPC, University Health Network, Toronto General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 9, 2005

Study Record Updates

• Last Update Posted (Estimate): July 19, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: HIV; non-alcoholic fatty liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Vitamin E; Antioxidants
• Other Study ID Numbers: 03-0297-B; ROGB139