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

Primary Purpose

Type 2 Diabetes, Nonalcoholic Steatohepatitis

Status
Terminated
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
sitagliptin
placebo
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.)

Sites / Locations

  • St. Joseph's Health Care

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

sitagliptin

placebo

Arm Description

sitagliptin 100mg/daily for 6 months

placebo match for 6 months

Outcomes

Primary Outcome Measures

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

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.
In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress.
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.

Full Information

First Posted
December 13, 2010
Last Updated
March 13, 2017
Sponsor
Lawson Health Research Institute
Collaborators
The Physicians' Services Incorporated Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01260246
Brief Title
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

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow recruitment
Study Start Date
December 2010 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lawson Health Research Institute
Collaborators
The Physicians' Services Incorporated Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sitagliptin
Arm Type
Experimental
Arm Description
sitagliptin 100mg/daily for 6 months
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo match for 6 months
Intervention Type
Drug
Intervention Name(s)
sitagliptin
Intervention Description
pill, 100mg/daily for 6 months
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo match for 6 months
Primary Outcome Measure Information:
Title
To demonstrate improvement in liver disease (based on liver biopsy)with sitagliptin.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
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
Title
In individuals with NASH and DM2: To delineate the effect of sitagliptin therapy on platelet aggregation and oxidative stress.
Time Frame
3 years
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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: 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). 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tisha Joy, MD
Organizational Affiliation
St. Joseph's Health Care, UWO
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Joseph's Health Care
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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