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

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ClinicalTrials.gov Identifier: NCT02263677
Recruitment Status : Withdrawn (Technical difficulties have caused this study to be terminated)
First Posted : October 13, 2014
Last Update Posted : October 5, 2016
Sponsor:
Information provided by (Responsible Party):
University of Missouri-Columbia

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.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Non-alcoholic Fatty Liver Disease Drug: Sitagliptin Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Project Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI
Study Start Date : March 2014
Estimated Primary Completion Date : December 2015
Actual Study Completion Date : January 2016


Arm Intervention/treatment
Experimental: Sitagliptin
60 day supply of 100mg Sitagliptin
Drug: Sitagliptin
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).
Other Name: Januvia




Primary Outcome Measures :
  1. Change in Liver steatosis [ Time Frame: baseline and Six months ]
    Steatosis measured by Magnetic Resonance Spectroscopy



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Type 2 diabetes mellitus with hemoglobin A1c above 6.5%.
  2. Waist circumference over 40 inches in a male or 35 inches in a female or BMI greater than 30.
  3. Age between 18 and 70 years.
  4. Stable on maximum tolerated dose of metformin for at least 3 months prior to enrollment.
  5. Sedentary (less than 30 minutes per week of structured activity) and weight stable (2% body weight in past 6 months).
  6. Metabolic syndrome based on NCEP ATP-3 guidelines with diabetes accepted as the glycemic component.
  7. 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.
  8. For men: surgically sterile or agreement that any female partner meet criteria of 7.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02263677


Locations
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United States, Missouri
University of Missouri-Columbia: Diabetes Center
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
University of Missouri-Columbia
Investigators
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Principal Investigator: Michael Gardner, MD University of Missouri-Columbia
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Responsible Party: University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT02263677    
Other Study ID Numbers: MERCK-9938
First Posted: October 13, 2014    Key Record Dates
Last Update Posted: October 5, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Missouri-Columbia:
diabetes
fatty liver
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action