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Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI

Primary Purpose

Type 2 Diabetes, Non-alcoholic Fatty Liver Disease

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Sitagliptin

About this trial

This is an interventional treatment trial for Type 2 Diabetes focused on measuring diabetes, fatty liver

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Type 2 diabetes mellitus with hemoglobin A1c above 6.5%.
Waist circumference over 40 inches in a male or 35 inches in a female or BMI greater than 30.
Age between 18 and 70 years.
Stable on maximum tolerated dose of metformin for at least 3 months prior to enrollment.
Sedentary (less than 30 minutes per week of structured activity) and weight stable (2% body weight in past 6 months).
Metabolic syndrome based on NCEP ATP-3 guidelines with diabetes accepted as the glycemic component.
For women: at least 2 years postmenopausal, surgically sterile, or using an acceptable contraceptive regimen to include OCP, IUD, double barrier, depo-provera, or subcutaneous progestin implant and negative urine pregnancy test at trial start.
For men: surgically sterile or agreement that any female partner meet criteria of 7.

Exclusion Criteria:

Pregnancy, breast feeding, or planning to become pregnant during the study period.
GFR less than 60mL per minute per meter squared.
Any medical condition expected to be terminal within one year.
Cirrhosis of any cause or liver disease due to auto-immune, infectious or alcohol induced hepatitis.
Active mental illness or other condition which in the opinion of the investigator would prevent informed consent or compliance with study protocol.
Use of PPAR agonist within six months prior to enrollment.
Daily insulin use.
Allergy or intolerance of sitagliptin or other DPP-4 inhibitor.
Use of DPP-4 inhibitor, bile acid sequesterant, or weight loss medications within three months prior to enrollment.
Significant alcohol use defined as greater than 21 standard servings of alcohol (10gms) per week for men and greater than 14 for women.
History of bariatric surgery or planned bariatric surgery during the study period.
Weight, girth, or other factor preventing MRI scanning.
Receipt of another study drug within 30 days of screening.
Unable to receive a DEXA scan due to participating in research study or medical procedure involving ionizing radiation exposure equivalent to a chest x-ray or greater in the past 12 months.

Sites / Locations

University of Missouri-Columbia: Diabetes Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sitagliptin

Arm Description

60 day supply of 100mg Sitagliptin

Outcomes

Primary Outcome Measures

Change in Liver steatosis

Steatosis measured by Magnetic Resonance Spectroscopy

Secondary Outcome Measures

Full Information

NCT ID

NCT02263677

First Posted

October 1, 2014

Last Updated

October 3, 2016

Sponsor

University of Missouri-Columbia

1. Study Identification

Unique Protocol Identification Number

NCT02263677

Brief Title

Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI

Official Title

Pilot Project Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Withdrawn

Why Stopped

Technical difficulties have caused this study to be terminated

Study Start Date

March 2014 (undefined)

Primary Completion Date

December 2015 (Anticipated)

Study Completion Date

January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Missouri-Columbia

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Participants will be persons with type 2 diabetes who are likely to have fatty liver disease. The investigators think that this medication will reduce fatty liver. The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication. The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions. This will be done 4 times. Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition). The goal of all of these studies is to determine whether the study drug lowers liver fat.

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) and finally cirrhosis is rapidly becoming the leading cause of liver injury and end stage liver disease, particularly in industrialized countries. Though several pharmacologic agents (i.e. metformin, pioglitazone and others) have been suggested to have benefit in reducing the progression of this disease, none is approved for use. The causes of NAFLD and NASH are unknown, though visceral obesity, metabolic syndrome and type 2 diabetes are recognized co-existent risk factors. Recent evidence has linked NAFLD to elevated dipeptidyl peptidase-4 (DPP-4). DPP-4 levels in the plasma and livers of persons with NAFLD are elevated and correlate with elevations in liver enzymes, though not with markers of insulin resistance alone. It has been proposed that increased DPP-4 activity in combination with decreased PPAR signaling stimulates the inflammatory response that leads to liver fibrosis in the transition of NASH to cirrhosis. Debate exists as to whether the effect of DPP-4 in the liver is via its effect on the intestinal hormones or its direct effects on liver tissue. Indeed some studies have found reductions in liver fat with administration of GLP-1 agonists in animal models of obesity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes, Non-alcoholic Fatty Liver Disease

Keywords

diabetes, fatty liver

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sitagliptin

Arm Type

Experimental

Arm Description

60 day supply of 100mg Sitagliptin

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Other Intervention Name(s)

Januvia

Intervention Description

60 day supply of 100mg Sitagliptin. The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication. The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions. This will be done 4 times. Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition).

Primary Outcome Measure Information:

Title

Change in Liver steatosis

Description

Steatosis measured by Magnetic Resonance Spectroscopy

Time Frame

baseline and Six months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Type 2 diabetes mellitus with hemoglobin A1c above 6.5%. Waist circumference over 40 inches in a male or 35 inches in a female or BMI greater than 30. Age between 18 and 70 years. Stable on maximum tolerated dose of metformin for at least 3 months prior to enrollment. Sedentary (less than 30 minutes per week of structured activity) and weight stable (2% body weight in past 6 months). Metabolic syndrome based on NCEP ATP-3 guidelines with diabetes accepted as the glycemic component. For women: at least 2 years postmenopausal, surgically sterile, or using an acceptable contraceptive regimen to include OCP, IUD, double barrier, depo-provera, or subcutaneous progestin implant and negative urine pregnancy test at trial start. For men: surgically sterile or agreement that any female partner meet criteria of 7. Exclusion Criteria: Pregnancy, breast feeding, or planning to become pregnant during the study period. GFR less than 60mL per minute per meter squared. Any medical condition expected to be terminal within one year. Cirrhosis of any cause or liver disease due to auto-immune, infectious or alcohol induced hepatitis. Active mental illness or other condition which in the opinion of the investigator would prevent informed consent or compliance with study protocol. Use of PPAR agonist within six months prior to enrollment. Daily insulin use. Allergy or intolerance of sitagliptin or other DPP-4 inhibitor. Use of DPP-4 inhibitor, bile acid sequesterant, or weight loss medications within three months prior to enrollment. Significant alcohol use defined as greater than 21 standard servings of alcohol (10gms) per week for men and greater than 14 for women. History of bariatric surgery or planned bariatric surgery during the study period. Weight, girth, or other factor preventing MRI scanning. Receipt of another study drug within 30 days of screening. Unable to receive a DEXA scan due to participating in research study or medical procedure involving ionizing radiation exposure equivalent to a chest x-ray or greater in the past 12 months.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Gardner, MD

Organizational Affiliation

University of Missouri-Columbia

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Missouri-Columbia: Diabetes Center

City

Columbia

State/Province

Missouri

ZIP/Postal Code

65212

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI

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