Iron Depletion Therapy for Type 2 DM and NAFLD

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Overall Status

Completed

CT.gov ID

NCT00230087

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Diabetes Mellitus	Procedure: blood donation	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histological evidence of NAFLD and enrollment in NASH CRN Database Study
Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo.
Hemoglobin HbA1c level ≤ 8 %
Serum ALT levels ≥1.3 x ULN
Between 18-65 years of age

Exclusion Criteria

Hereditary hemochromatosis or hepatic iron overload defined as any of the following:
2+ iron on hepatic iron staining
Hepatic Iron Index ≥ 1.9
C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype
Use of insulin or thiazolidinediones for the treatment of diabetes
Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics)
Serum ferritin <50μg/L
Serum transferrin-iron saturation <10 %
Hemoglobin <10 mg/L
Hematocrit <38 %
Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests)
Pregnant or lactating women
Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest.
Evidence of myocardial infarction as determined by an ECG