Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E
- Non-alcoholic fatty liver disease (NAFLD) is an excess accumulation of fat in the liver cells. It is associated with obesity, high blood pressure, high cholesterol, and diabetes. Some people with NAFLD only have excess fat in the liver. However, other people may develop a worse form of NAFLD with liver injury and scarring. This form, called non-alcoholic steatohepatitis (NASH), can lead to liver failure, liver cancer, and death. Not much is known about why some people develop NASH and others do not.
- Lifestyle changes such as diet, exercise, and weight loss can decrease the liver damage in NAFLD. Some studies show that vitamin E can also help treat NAFLD. The dose of vitamin E used in these studies is almost 40 times the recommended amount of vitamin E intake from food. It is unclear whether a lower dose could achieve the same effect. Researchers also want to study how vitamin E works at different doses to treat NAFLD.
- To find out the most effective dose of vitamin E to treat NAFLD.
- To gain a better understanding of how NAFLD and NASH develop, and predict who will respond to treatment.
- Individuals at least 18 years of age with suggestion of non-alcoholic fatty liver disease.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- For the first 12 weeks of the study, participants will meet with a nutritionist. They will have personalized diet and exercise plans. Treatment will be monitored with diaries and questionnaires to fill out at home. Participants will also wear a pedometer to measure physical activity.
- After the 12-week period, participants will have a full physical examination with the following tests:
- Blood tests
- Glucose tolerance tests
- Imaging studies (DEXA scan and magnetic resonance imaging)
- Liver and fatty tissue biopsy
- Two weeks after the tests, participants will start vitamin E treatment. They will take up to two pills a day, taken with fat-containing foods.
- 4 weeks after starting treatment they will have a repeat full evaluation with imaging tests, blood work, and liver and fat biopsies.
- Participants who are taking vitamin E will take it for up to 120 weeks. They will have monitoring visits every 8 to 12 weeks. At the end of 120 weeks, they will have another full evaluation, with imaging tests, blood work, and liver and fat biopsies.
Dietary Supplement: Vitamin E 200 IU/d
Dietary Supplement: Vitamin E 400 IU/d
Dietary Supplement: Vitamin E 800 IU/d
Behavioral: Diet and Exercise
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E|
- Biochemical: Percent of patients with normal transaminases at end of treatment. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Physiological: Absolute change in liver fat content by 1H-MRS [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Changes in hepatic and adipose tissue gene expression, oxidative stress and NH/NKT cell phenotype in response to treatment. [ Time Frame: 39 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||August 2018 (Final data collection date for primary outcome measure)|
Dietary Supplement: Vitamin E 200 IU/d
Non-alcoholic fatty liver disease (NAFLD) is the most common cause for liver test abnormalities in the western world, and an increasingly rising cause for liver-related morbidity and mortality. Vitamin E, a fat-soluble anti-oxidant was recently found to be an effective treatment for NAFLD; however, its mechanism of action is unclear. In a controlled clinical trial vitamin E treatment was shown to significantly reduce the hepatic fat burden, suggesting mechanisms other than reducing oxidative stress are involved. Furthermore, the optimal dose of vitamin E to treat NAFLD is unknown.
We propose a phase IIa study to determine the optimal dose of vitamin E and its mechanism and site of action. In this study we aim to enroll up to 90 patients with NAFLD. Initially, all patients will undergo 12 weeks of intensive lifestyle modification. Following that, all patients will be randomized to treatment with 3 different doses of natural vitamin E (rrr- -tocopherol at 200, 400 or 800 IU/d) for 24 weeks. The primary end points for efficacy are normalization of liver enzymes and reduction in liver fat contents by magnetic resonance spectroscopy. Patients will undergo liver and adipose tissue biopsies before vitamin E treatment and after 4 weeks of therapy, and the biopsy samples will be used to measure changes in gene expression and markers of oxidative stress. This will be coupled with extensive phenotyping before and after treatment using serological, radiological and dynamic endocrine testing and is aimed at finding the dose-response characteristics of vitamin E in NAFLD, and allowing us to understand the mechanism of its action.
After 24 weeks of randomized treatment, all patients will be switched to a dose of 800 IU/ml and will continue treatment for up to 30 months, at the end of which another liver biopsy will be performed. From this phase we will assess the effects of dose increase of vitamin E on liver enzymes and fat content, and will determine the effect of long-term treatment on histological outcome.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01792115
|Contact: Nevitt V Morris, R.N.||(301) firstname.lastname@example.org|
|Contact: Yaron Rotman, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Yaron Rotman, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|