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

• ClinicalTrials.gov Identifier: NCT00152815
• Recruitment Status: Terminated
• First Posted: September 9, 2005
• Last Update Posted: July 19, 2013
• Sponsor: Johane Allard
• Collaborator: Ontario HIV Treatment Network
• Information provided by (Responsible Party): Johane Allard, University Health Network, Toronto

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Fatty Liver	Drug: antioxidant vitamin E; Behavioral: weight reduction and exercise	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions
• Study Start Date: October 2003
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The change in grading of inflammation assessed by liver biopsy from month 0 to month 12 of the study [ Time Frame: month 0 and month 12 ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada, M5G 2C4

Sponsors and Collaborators

Johane Allard

Ontario HIV Treatment Network

Investigators

• Principal Investigator: Allard Johane, MD, FRCPC; University Health Network, Toronto General Hospital

More Information

• Responsible Party: Johane Allard, Gastroenterologist, Professor of Medicine, University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT00152815
• Other Study ID Numbers: 03-0297-B; ROGB139
• First Posted: September 9, 2005
• Last Update Posted: July 19, 2013
• Last Verified: July 2013

Keywords provided by Johane Allard, University Health Network, Toronto:

HIV; non-alcoholic fatty liver disease

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Vitamin E; Antioxidants; Vitamins; Micronutrients; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents