Fatty Liver Study in Patients With Type II Diabetes

Phase 4

Terminated

• Conditions: Nonalcoholic Fatty Liver; Type II Diabetes
• Interventions: Drug: Lantus insulin; Drug: DPP4 inhibitor; Drug: Pioglitazone

• Registration Number: NCT02365233
• Lead Sponsor: The University of Texas Medical Branch, Galveston

Brief Summary

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.

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 Timeline

• Study Start: 2013-05-01
• Study First Submitted: 2013-05-09
• Study First Submitted QC: 2015-02-17
• Study First Posted: 2015-02-18
• Primary Completion: 2016-12-31
• Study Completion: 2016-12-31
• Results First Submitted: 2018-03-08
• Status Verified: 2018-04
• Results First Submitted QC: 2018-07-05
• Last Update Submitted: 2018-07-05
• Results First Posted: 2018-07-31
• Last Update Posted: 2018-07-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lantus Insulin	Lantus insulin	0.35 U per kg body weight once daily
DPP4 inhibitor	DPP4 inhibitor	Sitagliptin, 100 mg/day or Saxagliptin, 5 mg/day
Thiazolidinedione	Pioglitazone	(Pioglitazone, 15 mg/day)

Primary Outcome Measures

Name	Time	Method
Change in Hepatic Lipid Content From Baseline Visit to Six 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.	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.

Trial Locations

Locations (1)

University of Texas Medical Branch -Galveston; 🇺🇸 Galveston, Texas, United States