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

NCT01260246 | Terminated

• 2 other identifiers: R-10-53317389
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin.

  3 years

Secondary Outcomes (3)

• 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

Study Arms (2)

sitagliptin

EXPERIMENTAL

sitagliptin 100mg/daily for 6 months

Drug: sitagliptin

placebo

PLACEBO COMPARATOR

placebo match for 6 months

Drug: placebo

Interventions

sitagliptin DRUG

pill, 100mg/daily for 6 months

sitagliptin

placebo DRUG

placebo match for 6 months

placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Alcohol consumption (\< 10g/day in women and \<20g/day in men)
• Cause of liver disease other than NAFLD (negative investigations for: viral hepatitis, iron overload, a-1 antitrypsin, ceruloplasmin, autoimmune disease)
• 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).

You may not qualify if:

• 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.)

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (1)

St. Joseph's Health Care

London, Ontario, N6A 4L6, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Tisha Joy, MD

  St. Joseph's Health Care, UWO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Endocrinology

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: December 15, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: March 14, 2017

Record last verified: 2017-03

Locations

CA (1)