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Iron Depletion Therapy for Type 2 DM and NAFLD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00230087
Recruitment Status : Completed
First Posted : September 30, 2005
Last Update Posted : November 7, 2012
Information provided by:
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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 2005
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Intervention Details:
  • Procedure: blood donation
    phlebotomy until iron depleted

Primary Outcome Measures :
  1. Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method [ Time Frame: one year ]
  2. (2) HOMA model- determined by the OGTT method [ Time Frame: one year ]

Secondary Outcome Measures :
  1. Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress [ Time Frame: one year ]
  2. Changes in intrahepatic and intraabdominal fat content as determined by CT scan [ Time Frame: one year ]
  3. Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2) [ Time Frame: one year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00230087

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United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Kris V Kowdley, MD University of Washington
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Responsible Party: Kris Kowdley MD, Virginia Mason Medical Center Identifier: NCT00230087    
Other Study ID Numbers: DK 61728-S1 (completed)
First Posted: September 30, 2005    Key Record Dates
Last Update Posted: November 7, 2012
Last Verified: November 2012
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases