Iron Depletion Therapy for Type 2 DM and NAFLD

Phase 2

Completed

• Conditions: Non-Alcoholic Fatty Liver Disease; Diabetes Mellitus

• Registration Number: NCT00230087
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. NAFLD can lead to severe liver disease in some patients. Patients with NAFLD develop resistance to the normal action of insulin. Insulin is important for processing sugar and fat and increased resistance to insulin leads to fat in the liver. There is a correlation between the amount of iron in a person's body and the ability of insulin to work properly. Several small studies suggest that removal of iron may improve both diabetes and NAFLD by lowering insulin resistance.

The goal of this pilot study is to determine the effect of iron depletion on insulin sensitivity in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This study will be performed as an ancillary P\&F study to the NASH CRN; all participants will be recruited from the NASH CRN Database Study. Secondary outcome measures will include the effect of iron depletion on hepatic necroinflammation, markers of oxidative stress and intrahepatic fat content. Insulin resistance will be directly measured using a two-step hyperinsulinemic euglycemic clamp procedure, before and after iron depletion by phlebotomy. Oral glucose tolerance tests will also be performed in order to evaluate the efficacy of using the indirect, but less cumbersome, HOMA model to derive values of insulin resistance in this patient cohort. This study will advance our understanding of the role of body iron stores in the pathophysiology of type 2 diabetes mellitus and non-alcoholic fatty liver disease. If iron depletion results in improved insulin sensitivity, reduced hepatic necroinflammation and/or intrahepatic fat content, a large scale, randomized, controlled trial of iron depletion in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease will be planned.

Study Timeline

• Study Start: 2005-09
• Study First Submitted: 2005-09-29
• Study First Submitted QC: 2005-09-29
• Study First Posted: 2005-09-30
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-06
• Last Update Posted: 2012-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method	one year
(2) HOMA model- determined by the OGTT method	one year

Secondary Outcome Measures

Name	Time	Method
Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress	one year
Changes in intrahepatic and intraabdominal fat content as determined by CT scan	one year
Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2)	one year

Trial Locations

Locations (1)

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States