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

NCT01963845 | Completed Phase 2 Results

• 1 other identifier: Sitagliptin-NAFLD
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF

  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.

  Baseline and 24 weeks

Secondary Outcomes (4)

• AST, Aspartate Aminotransferase

  Baseline and 24 weeks

• ALT, Alanine Aminotransferase

  Baseline and 24 weeks

• LDL, Low-density Lipoprotein

  Baseline and 24 weeks

• HOMA-IR, Homeostatic Model Assessment of Insulin Resistance

  Baseline and 24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Active drug

EXPERIMENTAL

Sitagliptin 100 mg

Drug: Sitagliptin

Interventions

Sitagliptin DRUG

Active drug

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at entry at least 18 years.
• Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men.
• Evidence of hepatic steatosis or liver fat (≥5%) by MRI.
• Prediabetic patients and controlled diabetic patients as defined by the ADA position statement on diabetes mellitus. Prediabetics have a HbA1c of 5.7 to 6.4 and controlled diabetic patients have an HbA1c between 6.4 and 8.0.
• Written informed consent.

You may not qualify if:

• Uncontrolled diabetes defined as a Hb A1c ≥ 8.0.
• Evidence of another form of liver disease.
• Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
• Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum.
• Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
• Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
• Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
• Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
• Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
• Drug-induced liver disease as defined on the basis of typical exposure and history.
• Bile duct obstruction as shown by imaging studies.
• History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year.
• Advanced liver disease: platelet counts \< 75,000/mm3 or prothrombin time \>16 seconds or history of bleeding disorders
• Decompensated liver disease, Child-Pugh score greater than or equal to 7 points
• History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92103, United States

Location

Related Publications (1)

• Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.

  PMID: 36318027 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Rohit Loomba, MD professor of Medicine
• Organization: University of California, San Diego

roloomba@ucsd.edu

858-543-2230

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Medicine

Study Record Dates

• First Submitted: October 11, 2013
• First Posted: October 16, 2013
• Study Start: January 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: October 20, 2016
• Results First Posted: October 20, 2016

Record last verified: 2016-10

Locations

US (1)