Nonalcoholic Steatohepatitis, Type 2 Diabetes
Conditions
Brief summary
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.
Interventions
DRUGsitagliptin
pill, 100mg/daily for 6 months
DRUGplacebo
placebo match for 6 months
Sponsors
The Physicians' Services Incorporated Foundation
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin. | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| In individuals with NASH and DM2: To document the impact of sitagliptin therapy on adipocytokines, inflammatory markers, non-traditional cardiovascular risk factors, adipose distribution, and dyslipidemia. | 3 years |
| In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress. | 3 years |
| In individuals with NASH and DM2: To determine the correlation between changes in histology with changes in hepatic fat demonstrated by MRI and changes in fibrosis by Fibroscan. | 3 years |
Countries
Canada
Outcome results
None listed