Iron Depletion Therapy for Type 2 DM and NAFLD
Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98195
- University of Washington Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Phlebotomy
Blood donation
|
phlebotomy until iron depleted
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method
Time Frame: one year
|
one year
|
|
(2) HOMA model- determined by the OGTT method
Time Frame: one year
|
one year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress
Time Frame: one year
|
one year
|
|
Changes in intrahepatic and intraabdominal fat content as determined by CT scan
Time Frame: one year
|
one year
|
|
Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2)
Time Frame: one year
|
one year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Kris V Kowdley, MD, University of Washington
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Endocrine System Diseases
- Metabolic Diseases
- Digestive System Diseases
- Glucose Metabolism Disorders
- Liver Diseases
- Fatty Liver
- Nutritional and Metabolic Diseases
- Diabetes Mellitus
- Non-alcoholic Fatty Liver Disease
- Health Services
- Health Care Facilities Workforce and Services
- Tissue and Organ Procurement
- Blood Donation
Other Study ID Numbers
- DK 61728-S1 (completed)
- U01DK061728 (U.S. NIH Grant/Contract)
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