Clinical trial NCT01260246: Sitagliptin for the Treatment of Non-alcoholic Steatohepatitis in Patients With Type 2 Diabetes
Official title: Sitagliptin for the Treatment of Non-alcoholic Steatohepatitis in Patients With Type 2 Diabetes.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Type 2 Diabetes
Nonalcoholic Steatohepatitis
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: The Physicians' Services Incorporated Foundation
First posted: 2010-12-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.)

Primary outcomes:
measure: To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin.
timeFrame: 3 years
Secondary outcomes:
measure: 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.
timeFrame: 3 years
measure: In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress.
timeFrame: 3 years
measure: 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.
timeFrame: 3 years
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: St. Joseph's Health Care, UWO
name: Tisha Joy, MD
role: PRINCIPAL_INVESTIGATOR
References: