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

Not Applicable

Terminated

• Conditions: Type 2 Diabetes; Nonalcoholic Steatohepatitis
• Interventions: Drug: sitagliptin; Drug: placebo

• Registration Number: NCT01260246
• Lead Sponsor: Lawson Health Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-13
• Study First Submitted QC: 2010-12-14
• Study First Posted: 2010-12-15
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-13
• Last Update Posted: 2017-03-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sitagliptin	sitagliptin	sitagliptin 100mg/daily for 6 months
placebo	placebo	placebo match for 6 months

Primary Outcome Measures

Name	Time	Method
To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin.	3 years

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

St. Joseph's Health Care; 🇨🇦 London, Ontario, Canada