Clinical trial NCT00152815: Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions
Official title: Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Fatty Liver
Keywords: HIV
non-alcoholic fatty liver disease
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Ontario HIV Treatment Network
First posted: 2005-09-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: The change in grading of inflammation assessed by liver biopsy from month 0 to month 12 of the study
timeFrame: month 0 and month 12
Secondary outcomes:
measure: Liver histology for steatosis and fibrosis staging
timeFrame: month 0 and month 12
measure: Liver immuno-histochemistry for adducts of MDA: a product of LP
timeFrame: month 0 and month 12
measure: Alpha-smooth muscle actin (alpha-SMA): a marker of hepatic stellate cell activation
timeFrame: month 0 and month 12
measure: Transforming growth factor (TGF-beta): a pro-fibrogenic cytokine involved in fibrogenesis
timeFrame: month 0 and month 12
measure: Liver lipid peroxides and TNP-alpha
timeFrame: month 0, month 6 and month 12
measure: Liver steatosis and volume will be assessed by ultrasound
timeFrame: month 0 and month 12
measure: Liver enzymes and IR (HOMA and QUICKY) will also be measured
timeFrame: month 0, month 6 and month 12
measure: Lipid peroxides, TNF-alpha, vitamin E and C in plasma
timeFrame: month 0, month 6 and month 12
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto General Hospital
name: Allard Johane, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: