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

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.

Conditions

• Nonalcoholic Steatohepatitis

Interventions

DRUG

pioglitazone-placebo

This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm following completion of the baseline measurements and continued on placebo for the rest of the clinical trial.

DRUG

pioglitazone

Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.

DIETARY_SUPPLEMENT

Vitamin E

All participants will receive vitamin E 400 IU orally twice daily.

DRUG

pioglitazone-placebo

This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm following completion of the baseline measurements and continued on placebo for the rest of the clinical trial.

DIETARY_SUPPLEMENT

Vitamin E

All participants will receive vitamin E 400 IU orally twice daily.

DRUG

Vitamin E-placebo

Placebo of vitamin E will be given to arm 3.

Sponsors & Collaborators

• VA Office of Research and Development

  lead FED

Principal Investigators

• Kenneth Cusi, PhD · North Florida/South Georgia Veterans Health System, Gainesville, FL

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-06-24

Primary Completion

2016-09-30

Completion

2016-12-31

Countries

• United States

Study Locations