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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01260246
• Other study ID #: R-10-533
• Secondary ID: 17389
• Status: Terminated
• Phase: N/A
• First received: December 13, 2010
• Last updated: March 13, 2017
• Start date: December 2010
• Est. completion date: April 2015

Study information

• Verified date: March 2017
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis
• Type 2 Diabetes

Intervention

Drug:
• sitagliptin
pill, 100mg/daily for 6 months
• placebo
placebo match for 6 months

Locations

Country	Name	City	State
Canada	St. Joseph's Health Care	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	The Physicians' Services Incorporated Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin.		3 years
Secondary	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
Secondary	In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress.		3 years
Secondary	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