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Effect of Iron Reduction by Phlebotomy for Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT02468037
Recruitment Status : Completed
First Posted : June 10, 2015
Last Update Posted : June 10, 2015
Sponsor:
Collaborators:
University of Colorado, Denver
University of New Mexico
Information provided by (Responsible Party):
Donald McClain, University of Utah

Brief Summary:
High tissue iron is a risk factor for diabetes even within the broad normal range of normal human values. In order to demonstrate the benefits of reducing iron on glucose homeostasis and to better define the parameters for larger clinical trials, the investigators will subject individuals with prediabetes (impaired glucose tolerance, IGT) or early type 2 diabetes to phlebotomy in order to reduce serum ferritin concentrations and determine the effect on glucose homeostasis as revealed by oral and frequently sampled intravenous glucose tolerance testing.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Prediabetes Procedure: Phlebotomy Not Applicable

Detailed Description:

Male and female subjects aged 35-65 will be recruited from the clinic populations at the Medical Centers of the Universities of Colorado, New Mexico, or Utah who have prediabetes, or diabetes relatively well-controlled (Hemoglobin A1c [HbA1c] ≤ 8.0%) with a single oral agent. Diabetes/prediabetes status is verified by oral glucose tolerance testing (OGTT) using criteria of the American Diabetes Association. Serum ferritin will be determined, and subjects chosen with values in the upper 50% of the normal range, 110-400 ng/mL for males, or 80-240 for females. Exclusion criteria include: hereditary hemochromatosis; cancer (except cases currently with no evidence of disease); serum creatinine >1.5; anemia (Hgb < lower limit of normal); chronic inflammatory conditions (rheumatologic conditions such as rheumatoid arthritis or giant cell arteritis, or chronic infections such as hepatitis B or C) that could affect ferritin; erythrocyte sedimentation rate or C-reactive protein>1.5 times the upper limit of normal (UNL); serum transaminases 2 x UNL; hemophilia, warfarin therapy, or history of GI bleeding; and current glucocorticoid therapy.

After determination of eligibility, subjects are randomized in a 2:1 ratio for treatment and controls arms. In the fasted state, blood is drawn for determination of adiponectin and lipids (HDL, direct LDL, triglycerides). Subjects have the option of participating in a frequently sampled intravenous glucose tolerance test (FSIVGTT). All subjects receive counseling to follow a healthy diet and regular exercise. Phlebotomy occurs at the rate of 500 ml (one Unit) of blood per month over the period of 3-6 months. At two-month intervals, serum ferritin and complete blood counts are determined. When serum ferritin reaches the lowest quartile of normal (<50 ng/mL for females and <70 ng/mL for males, but no sooner than 3 months or later than 6 months after beginning phlebotomy, metabolic status will be reassessed by fasting lipids, adiponectin, OGTT, and optionally, FSIVGTT. Controls are recalled for repeat testing 6-8 months after enrollment.

120 min OGTT and FSIVGTT are performed on separate days after an overnight fast. FSIVGTT data are analyzed using MINMOD Millennium software. Areas under the glucose curve (AUCglucose) are calculated using the trapezoidal method.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Iron Reduction by Phlebotomy for the Prevention and Treatment of Type 2 Diabetes
Study Start Date : April 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron

Arm Intervention/treatment
Experimental: Phlebotomy
All subjects receive counseling to follow a healthy diet and regular exercise. Phlebotomy occurs at the rate of 500 ml (one Unit) of blood per month over the period of 3-6 months. At two-month intervals, serum ferritin and complete blood counts are determined. When serum ferritin reaches the lowest quartile of normal (<50 ng/mL for females and <70 ng/mL for males, but no sooner than 3 months or later than 6 months after beginning phlebotomy, subjects will be retested for glucose tolerance as described
Procedure: Phlebotomy
Patients donate blood until tissue iron levels are in the lowest quartile of normal.

No Intervention: Control
Subjects receive counseling to follow a healthy diet and regular exercise.



Primary Outcome Measures :
  1. Improvement in glucose area under the curve. [ Time Frame: 6 months after initiation of phlebotomy ]
    As determined by oral glucose tolerance testing


Secondary Outcome Measures :
  1. Improvement in insulin sensitivity [ Time Frame: 6 months after initiation of phlebotomy ]
    As determined by intravenous glucose tolerance testing

  2. Improvement in insulin secretory capacity [ Time Frame: 6 months after initiation of phlebotomy ]
    As determined by intravenous glucose tolerance testing



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 35-65
  • Prediabetes, or diabetes relatively well-controlled (Hemoglobin A1c [HbA1c] ≤ 8.0%) with a single oral agent as defined by oral glucose tolerance testing (OGTT) using criteria of the American Diabetes Association.
  • Serum ferritin values in the upper 50% of the normal range, 110-400 ng/mL for males, or 80-240 for females.

Exclusion Criteria:

  • hereditary hemochromatosis;
  • cancer (except cases currently with no evidence of disease);
  • serum creatinine >1.5;
  • anemia (Hgb < lower limit of normal);
  • chronic inflammatory conditions (rheumatologic conditions such as rheumatoid arthritis or giant cell arteritis, or chronic infections such as hepatitis B or C) that could affect ferritin;
  • erythrocyte sedimentation rate or C-reactive protein>1.5 times the upper limit of normal (UNL);
  • serum transaminases 2 x UNL;
  • hemophilia,
  • warfarin therapy,
  • history of GI bleeding;
  • current glucocorticoid therapy.

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 ClinicalTrials.gov identifier (NCT number): NCT02468037


Sponsors and Collaborators
University of Utah
University of Colorado, Denver
University of New Mexico
Investigators
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Principal Investigator: Donald McClain, MD, PhD University of Utah

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Responsible Party: Donald McClain, M.D., University of Utah
ClinicalTrials.gov Identifier: NCT02468037     History of Changes
Other Study ID Numbers: IRB_00020094
First Posted: June 10, 2015    Key Record Dates
Last Update Posted: June 10, 2015
Last Verified: June 2015

Keywords provided by Donald McClain, University of Utah:
iron
diabetes
phlebotomy

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases