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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Lawson Health Research Institute.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
PSI Foundation inc
Information provided by:
Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT01260246
First received: December 13, 2010
Last updated: June 29, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Nonalcoholic Steatohepatitis
Drug: sitagliptin
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Sitagliptin for the Treatment of Non-alcoholic Steatohepatitis in Patients With Type 2 Diabetes.

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sitagliptin
sitagliptin 100mg/daily for 6 months
Drug: sitagliptin
pill, 100mg/daily for 6 months
Placebo Comparator: placebo
placebo match for 6 months
Drug: placebo
placebo match for 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260246

Contacts
Contact: Tisha Joy, MD 519-646-6296

Locations
Canada, Ontario
St. Joseph's Health Care Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Tisha Joy, MD FRCPC    519-646-6296    tisha.joy@sjhc.london.on.ca   
Contact: Melanie Beaton, MD FRCPC    519-663-3344    melanie.beaton@lhsc.on.ca   
Principal Investigator: Tisha Joy, MD, FRCPC         
Sub-Investigator: Melanie Beaton, MD FRCPC         
Sponsors and Collaborators
Lawson Health Research Institute
PSI Foundation inc
Investigators
Principal Investigator: Tisha Joy, MD St. Joseph's Health Care, UWO
  More Information

No publications provided

Responsible Party: Dr. Tisha Joy/ Principal Investigator, St. Joseph's Health Care, Department of Medicine, UWO
ClinicalTrials.gov Identifier: NCT01260246     History of Changes
Other Study ID Numbers: R-10-533, 17389
Study First Received: December 13, 2010
Last Updated: June 29, 2011
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Fatty Liver
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases
Sitagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014