Phase 2 N=22 Randomized Basic Science

Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E

Fatty Liver

Bottom Line

View on ClinicalTrials.gov: NCT01792115 ↗

Enrolled (actual)

Serious AEs

18.2%

Results posted

Oct 2020

Primary outcome: Primary: Biochemical: Number of Patients With Normal Transaminases at End of Treatment. — 6; 6; 6 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Vitamin E 200 IU/d (Drug); Vitamin E 400 IU/d (Drug); Vitamin E 800 IU/d (Drug); Diet and Exercise (Behavioral)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Primary completion: Aug 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Biochemical: Number of Patients With Normal Transaminases at End of Treatment.	6; 6; 6	—
PRIMARY Physiological: Absolute Change in Liver Fat	-1.9; -7.6; -0.6	—
SECONDARY Absolute Change in AST	-5.6; -1.8; -10.6	—
SECONDARY Percent Change in AST	-0.15; -0.07; -0.24	—
SECONDARY Absolute Change in ALT	-8; -8.3; -22	—
SECONDARY Percent Change in ALT	-0.17; -0.19; -0.35	—
SECONDARY Absolute Change in GGT	-6.1; -22.8; -11	—
SECONDARY Percent Change in Liver Fat	0.33; -0.42; -0.10	—

Summary

Background: * 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. Objectives: * 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. Eligibility: - Individuals at least 18 years of age with suggestion of non-alcoholic fatty liver disease. Design: * 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.

Eligibility Criteria

INCLUSION CRITERIA:

Clinical suspicion of NAFLD, defined by the presence of at least two of the following criteria:

Suggestion of liver fat by an imaging study (ultrasound, CT scan, MRI or MR spectroscopy) performed in the 6 months prior to enrollment.
Elevated aminotransferase levels (ALT > 31 U/L for men or > 19 U/L for women, or AST > 30 U/L) on at least two occasions in the 6 months preceding enrollment.
Presence of the metabolic syndrome, defined according to the modified AHA/NCEP criteria as the presence of at least three of:
Abdominal obesity, defined as waist circumference > 102 cm for men or > 88 cm for women
Elevated triglycerides (> 150 mg/dL) or the use of medication to lower triglycerides
Reduced HDL cholesterol ( 135/80 mmHg) or use of medication for hypertension
Elevated fasting glucose levels (> 100 mg/dL) or use of anti-diabetic medication
For the purpose of inclusion, the presence of overt diabetes mellitus type 2 will be considered equivalent to the presence of the metabolic syndrome, even if the other criteria are absent.
Estimated average alcohol consumption 18 years at enrollment
Willingness to participate in the study

EXCLUSION CRITERIA

Chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who were treated successfully for HCV and achieved sustained virological response can be eligible for enrollment > 18 months after treatment cessation. Patients who are inactive carriers of HBV (HBV DNA 0.5 g/dL, PT > 18, albumin = 1 year after intervention, can safely stop antiplatelet and anticoagulant medications before the performance of invasive procedures, and have adequate ventricular function as assessed by echocardiography or cardiology consultation. These patients will require cardiology consultation and clearance prior to enrollment.
Congestive heart failure.
Chronic kidney disease, with creatinine clearance = 3 seconds from the upper limit of the normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (<70,000), or platelet dysfunction will not be enrolled because of potential increase in risk of bleeding with vitamin E treatment. Antiplatelet agents taken for cardiovascular prevention will not exclude patients, unless they cannot be stopped safely for the performance of a liver biopsy.
Maldigestion or malabsorption that can interfere with absorption of vitamin E including: steatorrhea of all causes, chronic pancreatitis, cystic fibrosis, short bowel syndrome, severe cholestasis, orlistat treatment and similar conditions
Inability to swallow vitamin E capsules
Allergy to vitamin E
Alcohol or substance abuse within the past 12 months. Patients will be required to have an AUDIT score of 7 or less18, and drink no more than 14 drinks/week (for men) or 7 drinks/week (for women).
For women of childbearing age, pregnancy or inability (or unwillingness) to practice contraception for the duration of the study or breast feeding.
Inability to understand and give informed consent for participation.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01792115). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.