Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanics With Diabetes Mellitus Type 2 (T2DM) and Role of Treatment

• Status: Completed
• Trial end date: 2016-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition frequently associated with type 2 diabetes (T2DM) and characterized by insulin resistance and hepatic fat accumulation. Liver fat may range from simple steatosis to severe steatohepatitis with necroinflammation and variable degrees of fibrosis (nonalcoholic steatohepatitis or NASH). Up to 40% of patients with NAFLD develop NASH in recent series. Risk factors for progression to NASH are unclear, but appears to be more common and progress more rapidly in older individuals, and in the presence of obesity and T2DM. Because the VA population in San Antonio, Texas, frequently combine these risk factors for NASH it was felt that a study targeting this very high-risk population was needed.

This study will establish the long-term efficacy (primary endpoint: liver histology) and safety of pioglitazone for the treatment of VA patients with T2DM and NASH. All patients diagnosed with NASH will be offered lifestyle modification/weight loss (current standard of care) while being randomized to pioglitazone, vitamin E or placebo for up to 3 years. We believe that in such a high-risk population for complications from NASH, a substantial benefit may be expected from early detection and treatment.

Specifically, the arms are: a) pioglitazone + vitamin E; b) vitamin E + placebo of pioglitazone; c) placebo of both. Patients are randomized to one of these 3 arms, and followed in a double-blind fashion for up to 18 months. Patients are then offered to continue into an open-label phase with pioglitazone + vitamin E or vitamin E alone for another 18 months.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Treatments: alpha-Tocopherol; Pioglitazone; Tocopherols; Tocotrienols; Vitamin E; Vitamins

Criteria

Inclusion Criteria:

• Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent.

• Subjects of both genders from within the Veterans Administration Healthcare System with an age range between 18 to 70 years (inclusive).

• Have type 2 diabetes mellitus as defined by the American Diabetes Association guidelines.

• Female volunteers must be non-lactating and must either be at least one year post-menopausal, or be using adequate mechanical contraceptive precautions (i.e. intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period.

• The following laboratory values:

• Hemoglobin at least 12 gm/dl in males or 11 gm/dl in females, WBC count 3,000/mm3 (neutrophil count 1,500/mm3) and platelets 100,000/mm3

• Albumin equal or greater than 3.0 g/dl

• Serum creatinine less than 1.8 mg/dl

• AST and ALT up to 3.0 times upper limit of normal and alkaline phosphatase 2.5 times ULN

Exclusion Criteria:

• Any cause of chronic liver disease other than NASH (such as -but not restricted to- alcohol or drug abuse, medication, chronic hepatitis B or C, autoimmune, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency).

• Any clinical evidence or history of ascitis, bleeding varices, or spontaneous encephalopathy.

• History of alcohol abuse (alcohol consumption greater than 20 grams of ethanol per day) or a positive AUDIT screening questionnaire.

• Prior surgical procedures to include gastroplasty, jejunoileal or jejunocolic bypass.

• Prior exposure to organic solvents such as carbon tetrachloride.

• Total parenteral nutrition (TPN) within the past 6 months.

• Subjects with type 1 diabetes mellitus.

• Patients on chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for 4 weeks before entry into the study.

• Patients on drugs known to cause hepatic steatosis: estrogens or other hormonal replacement therapy, tamoxifen, raloxifene, oral glucocorticoids, chloroquine and others.

• Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II), peripheral vascular disease (history of claudication), or diagnosed pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation).

• Patients with severe osteoporosis (-3.0 at the level of spine and hip).

• Patients who have clinically significant acute or chronic medical conditions not specifically written in the protocol, but that based in the investigator's clinical judgment he/she considers unlikely that he will be able to complete study participation or that such participation may be potentially detrimental to his well-being.