Sitagliptin for the Treatment of Non-alcoholic Steatohepatitis in Patients With Type 2 Diabetes

Lawson Health Research Institute

Status

Terminated

Conditions

Type 2 Diabetes

Nonalcoholic Steatohepatitis

Treatments

Drug: sitagliptin

Drug: placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT01260246

R-10-533

17389 (Registry Identifier)

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled trial evaluating the impact of sitagliptin therapy in patients with concomitant type 2 diabetes and non-alcoholic steatohepatitis (NASH) on improving liver disease based on biopsy results. The effect of sitagliptin on other measures such as hormones modifying insulin release and sensitivity (termed adipocytokines), fat distribution, and biomarkers of cardiovascular risk will also be evaluated.

Enrollment

12 patients

Sex

All

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Known DM2 (receiving lifestyle management and/or metformin and/or sulfonylurea
Stable therapy for DM2 for the past 3 months
All other medications and doses stable for past 3 months
HbA1c 8.9% or lower (can be done in past 30 days)
Known NASH based on the accepted American Gastroenterological Association Criteria:
1. Alcohol consumption (< 10g/day in women and <20g/day in men)
2. Cause of liver disease other than NAFLD (negative investigations for: viral hepatitis, iron overload, a-1 antitrypsin, ceruloplasmin, autoimmune disease)
3. Liver histology demonstrating macrovesicular fatty change of hepatocytes, with evidence of steatohepatitis, manifested by the presence of Mallory Bodies, ballooning degeneration, lobular neutrophilic inflammation and perisinusoidal fibrosis. (If liver biopsy done within 2 years prior to screening for this trial, that biopsy will be reviewed to ensure it meets criteria for diagnosis).

Exclusion criteria

Any contraindication for undergoing MRI
Child class B or C cirrhosis
Participation in another clinical trial
Use of thiazoledinedione (rosiglitazone or pioglitazone) in past 6 months
Current use of plavix
Previous exposure to sitagliptin
Prior history of pancreatitis
History of anaphylaxis to another Canadian-marketed DPP-IV inhibitor (saxagliptin)
Creatine clearance <30 ml/min
Anaemia (haemoglobin < 110 mg/dL)
Platelet count < 50 000 cells/mm3
Known heart or kidney failure
Comorbid condition that decreases natural life span (e.g. known cancer)
Pregnant or breastfeeding or wishing to become pregnant in the next 6 months
Current or past treatment with medications that can induce steatohepatitis (e.g. glucocorticoids, methotrexate, amiodarone etc.)