Fatty Liver Study in Patients With Type II Diabetes

• ClinicalTrials.gov Identifier: NCT02365233
• Recruitment Status: Terminated
• First Posted: February 18, 2015
• Results First Posted: July 31, 2018
• Last Update Posted: July 31, 2018
• Sponsor: The University of Texas Medical Branch, Galveston
• Information provided by (Responsible Party): The University of Texas Medical Branch, Galveston

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type II Diabetes; Nonalcoholic Fatty Liver	Drug: DPP4 inhibitor; Drug: Pioglitazone; Drug: Lantus insulin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: December 31, 2016
• Actual Study Completion Date: December 31, 2016

Arms and Interventions

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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in Hepatic Lipid Content From Baseline Visit to Six Month Follow up Visit [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

University of Texas Medical Branch -Galveston

Galveston, Texas, United States, 77555

Sponsors and Collaborators

The University of Texas Medical Branch, Galveston

Investigators

• Principal Investigator: Nicola Abate, MD; University of Texas Medical Branch-Galveston

More Information

• Responsible Party: The University of Texas Medical Branch, Galveston
• ClinicalTrials.gov Identifier: NCT02365233
• Other Study ID Numbers: 13-021
• First Posted: February 18, 2015
• Results First Posted: July 31, 2018
• Last Update Posted: July 31, 2018
• Last Verified: April 2018

Keywords provided by The University of Texas Medical Branch, Galveston:

Type II Diabetes; Nonalcoholic fatty liver

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases; Insulin; Insulin, Globin Zinc; Pioglitazone; Sitagliptin Phosphate; Insulin Glargine; Saxagliptin; Dipeptidyl-Peptidase IV Inhibitors; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action