Iron Depletion Therapy for Type 2 DM and NAFLD - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00230087

Purpose

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	Intervention	Phase
Non-Alcoholic Fatty Liver Disease Diabetes Mellitus	Procedure: blood donation	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Iron Liver Diseases

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method [ Time Frame: one year ] [ Designated as safety issue: No ]
(2) HOMA model- determined by the OGTT method [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress [ Time Frame: one year ] [ Designated as safety issue: No ]
Changes in intrahepatic and intraabdominal fat content as determined by CT scan [ Time Frame: one year ] [ Designated as safety issue: No ]
Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2) [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	September 2005
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Intervention Details:

phlebotomy until iron depleted

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00230087

Locations

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)

Investigators

Principal Investigator:

Kris V Kowdley, MD

University of Washington

More Information

No publications provided

Responsible Party:	Kris Kowdley MD, Virginia Mason Medical Center
ClinicalTrials.gov Identifier:	NCT00230087 History of Changes
Other Study ID Numbers:	DK 61728-S1
Study First Received:	September 29, 2005
Last Updated:	August 3, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

diabetes
nafld
nash
phlebotomy

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Fatty Liver
Liver Diseases

Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on February 09, 2012