Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease

Phase 2

Completed

Conditions: Non-alcoholic Fatty Liver Disease

Interventions: Drug: Placebo
Drug: Sitagliptin

Registration Number: NCT01963845

Lead Sponsor: University of California, San Diego

Brief Summary: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.

Detailed Description: Primary objectives:

1. To examine the efficacy of sitagliptin 100 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with NAFLD.

Secondary objectives:

1. To examine the efficacy of sitagliptin in improving serum AST in patients with NAFLD.

2. To examine the efficacy of sitagliptin in improving serum ALT in patients with NAFLD.

3. To examine the efficacy of sitagliptin in improving serum LDL in patients with NAFLD.

4. To examine the efficacy of sitagliptin in the improvement of insulin sensitivity in patients with NAFLD.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Active drug	Sitagliptin	Sitagliptin 100 mg

Primary Outcome Measures

Name	Time	Method
Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF	Baseline and 24 weeks	Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.

Secondary Outcome Measures

Name	Time	Method
AST, Aspartate Aminotransferase	Baseline and 24 weeks	AST, measured in IU/L at baseline and 24 weeks
ALT, Alanine Aminotransferase	Baseline and 24 weeks	ALT, measured in IU/L at baseline and 24 weeks
LDL, Low-density Lipoprotein	Baseline and 24 weeks	LDL, measured in mg/dL at baseline and 24 weeks
HOMA-IR, Homeostatic Model Assessment of Insulin Resistance	Baseline and 24 weeks	HOMA-IR, calculated as \[(glucose (mg/dL) X insulin (mg/dL)) / 405 \] at baseline and 24 weeks