- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01963845
Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease
Study Overview
Status
Conditions
Intervention / Treatment
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:
- To examine the efficacy of sitagliptin in improving serum AST in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum ALT in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum LDL in patients with NAFLD.
- To examine the efficacy of sitagliptin in the improvement of insulin sensitivity in patients with NAFLD.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92103
- University of California, San Diego
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
44 patients with NAFLD will be randomized to either sitagliptin or placebo for 24-weeks. Enrollment of 50 patients is needed to allow for exclusion of some patients after initial evaluation and a dropout of a small number of patients because of intolerance to sitagliptin.
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
- Recent initiation or change of anti-diabetic drugs, including insulin, sulfonylureas, or thiazolidinediones in the previous 90 days.
- Use of sitagliptin or other agents in the same class within the 90 days prior to randomization.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with Sitagliptin and adequate follow up.
- History of acute pancreatitis within the last 5 years with the exception of gallstone pancreatitis.
- Positive test for anti-HIV.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
- Pregnancy or inability to practice adequate contraception in women of childbearing potential.
- Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer.
- Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibility hinder completion of the study.
- Serum creatinine >1.5 mg/dl.
Contraindications to Sitagliptin use :
- History of allergic reaction to Sitagliptin
- Patients with acute liver injury or unexplained persistent elevations in ALT > 500 U/L at baseline.
- Women who are pregnant or may become pregnant
- Nursing mothers
Contraindications to MRI:
- The subject has any contraindication to MR imaging, such as patients with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field.
- The subject has a history of extreme claustrophobia
- The subject cannot fit inside the MR scanner cavity
11. RECRUITMENT Enrollment of patients may be initiated once IRB approval is acquired and will continue until June 2015.
Patients will be recruited from the following populations:
- Primary care and internal medicine clinics
Tertiary referral clinics at the Hillcrest Campus and Perlman Clinics:
- GI/Liver clinic
- Liver transplant clinic
- Obesity clinic
- Bariatric surgery clinic
- Diabetes clinic
- Lipid disorders clinic
- Physicians taking care of the patients would provide information regarding the study and then either refer the patient to our clinic or ask the patient to directly contact the PI or research assistant.
- Patient would be given information regarding possible studies in NAFLD in liver clinic by their providers. We would ask the patient to call or email the PI or research assistant to further discuss the study, if they are interested.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
|
Experimental: Active drug
Sitagliptin 100 mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF
Time Frame: 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.
|
Baseline and 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AST, Aspartate Aminotransferase
Time Frame: Baseline and 24 weeks
|
AST, measured in IU/L at baseline and 24 weeks
|
Baseline and 24 weeks
|
ALT, Alanine Aminotransferase
Time Frame: Baseline and 24 weeks
|
ALT, measured in IU/L at baseline and 24 weeks
|
Baseline and 24 weeks
|
LDL, Low-density Lipoprotein
Time Frame: Baseline and 24 weeks
|
LDL, measured in mg/dL at baseline and 24 weeks
|
Baseline and 24 weeks
|
HOMA-IR, Homeostatic Model Assessment of Insulin Resistance
Time Frame: Baseline and 24 weeks
|
HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks
|
Baseline and 24 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Liver Diseases
- Fatty Liver
- Non-alcoholic Fatty Liver Disease
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Sitagliptin Phosphate
Other Study ID Numbers
- Sitagliptin-NAFLD
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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