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

This study has been terminated.
(Not enough eligible patients available)
Sponsor:
Collaborator:
Ontario HIV Treatment Network
Information provided by (Responsible Party):
Johane Allard, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00152815
First received: September 7, 2005
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
HIV Infections
Fatty Liver
Drug: antioxidant vitamin E
Behavioral: weight reduction and exercise
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Liver histology for steatosis and fibrosis staging [ Time Frame: month 0 and month 12 ] [ Designated as safety issue: No ]
  • Liver immuno-histochemistry for adducts of MDA: a product of LP [ Time Frame: month 0 and month 12 ] [ Designated as safety issue: No ]
  • Alpha-smooth muscle actin (alpha-SMA): a marker of hepatic stellate cell activation [ Time Frame: month 0 and month 12 ] [ Designated as safety issue: No ]
  • Transforming growth factor (TGF-beta): a pro-fibrogenic cytokine involved in fibrogenesis [ Time Frame: month 0 and month 12 ] [ Designated as safety issue: No ]
  • Liver lipid peroxides and TNP-alpha [ Time Frame: month 0, month 6 and month 12 ] [ Designated as safety issue: No ]
    For oxidative stress and inflammation in the liver

  • Liver steatosis and volume will be assessed by ultrasound [ Time Frame: month 0 and month 12 ] [ Designated as safety issue: Yes ]
  • Liver enzymes and IR (HOMA and QUICKY) will also be measured [ Time Frame: month 0, month 6 and month 12 ] [ Designated as safety issue: Yes ]
  • Lipid peroxides, TNF-alpha, vitamin E and C in plasma [ Time Frame: month 0, month 6 and month 12 ] [ Designated as safety issue: No ]
    Parameters for oxidative stress and antioxidant capacity


Enrollment: 30
Study Start Date: October 2003
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00152815

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

No publications provided

Responsible Party: Johane Allard, Gastroenterologist, Professor of Medicine, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00152815     History of Changes
Other Study ID Numbers: 03-0297-B, ROGB139
Study First Received: September 7, 2005
Last Updated: July 17, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
HIV
non-alcoholic fatty liver disease

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Fatty Liver
HIV Infections
Liver Diseases
Digestive System Diseases
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Alpha-Tocopherol
Antioxidants
Tocopherols
Tocotrienols
Vitamin E
Vitamins
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 30, 2014