Fatty Liver Study in Patients With Type II Diabetes

A Phase IV, Open Label, Randomized Trial on the Effect of Metformin Plus Lantus Insulin, Pioglitazone, or DPP4 Inhibitor on Fatty Liver in Patients With Type II Diabetes

The primary objective of this trial is to measure changes in hepatic lipid content using three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.

Study Overview

• Status: Terminated
• Conditions: Type II Diabetes; Nonalcoholic Fatty Liver
• Intervention / Treatment: Drug: Pioglitazone; Drug: Lantus insulin; Drug: DPP4 inhibitor

Detailed Description

In patients with type 2 diabetes whose glycemic control is not accomplished with Metformin alone, there are several options for additional hypoglycemic agent. As per recent National guidelines at least three "second line" agents can be added to metformin: thiazolidinediones, Lantus insulin, and DPP4 inhibitors. All three approaches have been proven to help accomplishing goals of therapy for glycemic control (HbA1c<7%) in clinical trials. Whether one approach is superior to the other in improving associated non-glycemic metabolic abnormalities and risk for future morbidity and mortality in patients with type 2 diabetes remains a matter of intense debate. Among these abnormalities, excessive triglyceride content in the liver (fatty liver or liver steatosis) is a major predictor of risk for non-alcoholic steato-hepatitis (NASH) and liver cirrhosis. Fatty liver is highly prevalent in patients with type 2 diabetes. There are no clinical studies done to determine if any of these three therapeutic options is superior at reducing the liver triglyceride content in patients with type 2 diabetes and fatty Liver. Therefore, in this study we propose to measure and compare the effects on liver triglyceride content when either pioglitazone, lantus insulin, or DPP4 inhibitors are added to metformin in patients with poorly controlled type 2 diabetes (HbA1c>7.6%) and fatty liver (presence of "bright" liver in abdominal ultrasound). The primary objective of this trial is to measure changes in hepatic lipid content using three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch -Galveston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has provided informed consent in a manner approved by the Institutional Review Board (IRB) and is willing and able to comply with the trial procedures.
2. Adults at least 18 years of age at the time of consent.
3. Have type 2 diabetes mellitus.
4. Be on a stable medication with metformin (2000 mg/day) for at least 3 months prior to study enrollment.
5. Have blood A1c >7.6% and < 8.5% within 3 months prior to study enrollment.
6. Have fatty liver, which is diagnosed by ultrasonographic findings of "bright liver" within 1 year of study enrollment.
7. Stable medication for lipid lowering, blood pressure control, dietary supplements, including vitamins, for at least 3 months.
8. Women of Childbearing Potential must be willing and able to use acceptable forms of birth control while on the study.

Exclusion Criteria:

1. Currently taking medication that can affect glucose metabolism other than Metformin.
2. History of Kidney diseases that, in the opinion of the investigator , would place the subject at increased risk of participation or plasma levels of creatinine > 1.4 for women and > 1.5 for men.
3. History of Cirrhosis of liver, hepatitis, or other liver diseases that, in the opinion of the investigator, would place the subject at increased risk of participation.
4. Current alcohol consumption more than12 to 15 g of alcohol a day, or >12 oz of beer, 5 oz of wine, or 1.5 oz of distilled spirits.
5. History of heart failure.
6. Concurrent participation on another research study
7. Use of an investigational agent in the 30 days prior to signing informed consent.
8. History of prior non-compliance or the presence or history of psychiatric conditions (including drug or alcohol addiction) that would, in the opinion of the investigator, make it difficult for the subject to comply with the study procedures or follow the investigators instructions.
9. Females who are pregnant or lactating
10. Current Diagnosis or History of Bladder Cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Thiazolidinedione; (Pioglitazone, 15 mg/day)	Drug: Pioglitazone; Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.; Other Names: Pioglitazone 15 mg daily
ACTIVE_COMPARATOR: Lantus Insulin; 0.35 U per kg body weight once daily	Drug: Lantus insulin; Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.; Other Names: Lantus insulin (0.35U/kg of body weight once daily)
ACTIVE_COMPARATOR: DPP4 inhibitor; Sitagliptin, 100 mg/day or Saxagliptin, 5 mg/day	Drug: DPP4 inhibitor; Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.; Other Names: sitagliptin100 mg daily; saxagliptin 5 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hepatic Lipid Content From Baseline Visit to Six Month Follow up Visit	Comparison of the hepatic lipid content measurement taken by MRI at baseline with the measurement taken by MRI at the 6 month follow up visit.	Hepatic lipid content measurement will be taken on Day #1 ( the day of randomization) and at the 6 month follow up visit.

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Nicola Abate, MD, University of Texas Medical Branch-Galveston

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2013
• Primary Completion (ACTUAL): December 31, 2016
• Study Completion (ACTUAL): December 31, 2016

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: February 17, 2015
• First Posted (ESTIMATE): February 18, 2015

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Type II Diabetes; Nonalcoholic fatty liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Insulin; Insulin, Globin Zinc; Insulin Glargine; Pioglitazone; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Saxagliptin
• Other Study ID Numbers: 13-021