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Iron Reduction for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03696797
Recruitment Status : Recruiting
First Posted : October 5, 2018
Last Update Posted : September 28, 2022
Sponsor:
Collaborators:
University of North Carolina, Chapel Hill
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Study Description
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Brief Summary:
This is a treatment study to determine if reducing the body's iron stores by blood donation will improve diabetes control and other problems associated with diabetes such as fatty liver disease.

Condition or disease Intervention/treatment Phase
Iron Diabetes Nonalcoholic Fatty Liver Procedure: Blood Donation Procedure: Sham Blood Donation Not Applicable

Detailed Description:

Investigators propose that high iron triggers a number of events in different tissues, some of which will predispose to diabetes. Investigators will therefore study normal individuals who have higher than average iron levels in tissues, test your glucose control through standard blood tests like the hemoglobin A1c and by placing a continuous glucose monitor before and after participants have donated blood to determine if decreasing iron levels had any effect.

In addition, iron may also play a role in the progression of fatty liver to scarring and cirrhosis. Since 75% of people with diabetes have some degree of fatty liver, investigators would also like to study how the liver reacts to the lowering of iron.

There will be two optional sub studies conducted only at Wake Forest University Health Sciences they are: 1) Liver substudy that will look at liver complication of diabetes and the role it plays in the progression of fatty liver to scarring and cirrhosis. Investigators will look at how liver reacts to the lowering of iron. 2)Glucose Tolerance Mechanism substudy that will look at the mechanism the body uses to regulate blood sugar levels by insulin, this will require the frequently sample intravenous glucose tolerance test (FSIVGTT).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Both groups will not know assignment as all will have a sleep mask (like a blindfold, covering the eyes, held on with an elastic band) placed so participant will not know whether blood was actually removed.
Primary Purpose: Treatment
Official Title: Iron Reduction by Phlebotomy for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Treatment Group
Will have a Unit of blood (two cups, the same amount donated at the Red Cross) drawn. This involves having a needle inserted into a vein in your arm. Prior to taking the blood, staff will measure your blood count to be sure you are not anemic, and blood pressure to be sure no dehydration. During or after donation, a sports drink is provided to replace the fluid loss. Phlebotomy
 Procedure: Blood Donation
Participants in the TREATMENT GROUP will have a Unit of blood (two cups, the same amount you would donate at the Red Cross) drawn. This involves having a needle inserted into a vein in your arm. Prior to taking the blood, staff will measure blood count to be sure participants are not anemic, and blood pressure to be sure there is no dehydration. During or after donation, participants will be given a sports drink to replace the fluid loss. Participants in the CONTROL GROUP will not donate blood, but will have a needle inserted into a vein in your arm. Neither group will not know to which they have been assigned, all will have a sleep mask (like a blindfold, covering the eyes, held on with an elastic band) placed so they will not know whether blood was actually removed.
Sham Comparator: Control Group
Will not donate blood, but will have a needle inserted into a vein in your arm. Both groups will not know which group assignment they have been randomized. Sham Phlebotomy
 Procedure: Sham Blood Donation
Participants will have a needle inserted their arm, however, no blood will be drawn.


Outcome Measures
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Primary Outcome Measures :
  1. Change in HgbA1C [ Time Frame: Baseline, Month 6 ]
    Change in glycemia as measured byHgbA1C. Values from baseline and month 6 will be reported.

  2. Change in ALT [ Time Frame: Baseline, Month 12 ]
    ALT values from baseline and month 12 will be reported.

  3. Change in FSIGTT DI (Frequently sampled intravenous glucose tolerance test) [ Time Frame: Baseline, Month 6 ]
    FSIGTT DI Values from baseline and month 6 will be reported.


Secondary Outcome Measures :
  1. HgbA1C at Month 12 [ Time Frame: Month 12 ]
    HgbA1C values will be reported.

  2. Change in fasting glucose [ Time Frame: Month 6, Month 12 ]
    Fasting glucose measured on glucose machine (Abbott Freestyle Libre Pro system). Values of month 6 and month 12 will be reported.

  3. Change in HOMA-IR (Homeostatic Model Assessment-Insulin Resistance) [ Time Frame: Baseline, 12 months ]
    Insulin sensitivity measured by HOMA-IR (Homeostatic Model Assessment-Insulin Resistance) calculated from fasting glucose and insulin. Values will be reported for Baseline and 12 months.

  4. Number of participants that Discontinued of oral antihyperglycemic agent [ Time Frame: Month 12 ]
    The numbers of participants that discontinued of oral antihyperglycemic agents

  5. Change in Weight [ Time Frame: Baseline, Month 12 ]
    The change in weight from baseline to month 12 will be reported

  6. Change in Blood Pressure [ Time Frame: Baseline, Month 12 ]
    The change in Blood pressure from baseline to month 12 will be reported

  7. Number of participants that converted from pre-diabetes to Diabetes [ Time Frame: Month 12 ]
    Number of participants that converted from pre-Diabetes to Diabetes based on the HbA1C criteria.

  8. Number of participants that converted from pre-diabetes to normal glucose tolerance [ Time Frame: Month 12 ]
    Number of participants that converted from pre-Diabetes to normal glucose tolerance based on the HbA1C criteria.


Eligibility Criteria
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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 40-75
  • At least 3 months since diagnosis of prediabetes or diabetes
  • HgbA1C value within three months or at screening of 5.7-6.4% for those with prediabetes and 7- 8.5% for those with diabetes (the upper limit of the latter to reduce the likelihood of major changes in glycemic intervention during the trial period, and the lower limit to allow some room for improvement)
  • Undiagnosed on no medication HgA1C 6.5-6.9
  • C-reactive protein levels up to 11.0
  • Aim 2-serum ALT> 1.5 times the upper limit of normal, or; liver stiffness of > 12.5 kPa by Fibroscan transient elastography
  • Serum ferritin levels within 1 year or at the time of screening in the upper half of the normal range (>50 ng/mL for women; >100ng/mL for men)

Exclusion Criteria:

  • Documented anemia
  • Hemoglobin levels within 0.5 g/dL of the lower limit of normal (<12.5 g/dL for women; 13.5 g/dL for men)
  • Recent blood loss
  • Bleeding diatheses (coagulation abnormalities or treatment with anticoagulants)
  • Serious chronic infections or chronic inflammatory conditions that could elevate ferritin as an "acute phase reactant
  • C-reactive protein greater than the upper limit of normal to further validate the lack of significant chronic inflammation
  • Active cancer diagnosis (excluding skin cell cancers other than melanoma)
  • Renal insufficiency (eGFR<60 ml/min)
  • History of orthostatic hypotension
  • Heavy alcohol use (NIH criteria for men, greater than 4 drinks on any day or 14/week)
  • Pregnancy or premenopausal women of childbearing age, unless unable to become pregnant because of oral contraceptive use or surgical loss of ovaries or uterus
  • Aim 2 - individuals meeting the additional inclusion criteria for aim 2 will be tested for anti-HAV IgM, HBs Ag, anti-HBc. IgM, anti HCV IgM and IgG. Subjects who prove positive for any of these viral serologies, except for HCV IgG will be excluded. The latter will be tested for HCV RNA by PRC, and if negative they will be eligible for enrollment
Contacts and Locations
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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): NCT03696797


Contacts
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Contact: Donald A McClain, MD, Ph.D 336-716-7782 dmcclain@wakehealth.edu
Contact: Audrey Bell-Farrow, MBA, MHA 336-713-0370 abellfa@wakehealth.edu

Locations
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United States, North Carolina
University of North Carolina at Chapel Hill (UNC) Recruiting
Chapel Hill, North Carolina, United States, 27599-2100
Contact: John Buse, MD, Ph.D    919-966-0134    John_buse@med.unc.edu   
Contact: Laura Young, MD    (919) 966-3465    Laura_Young@med.unc.edu   
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Donald A McClain, MD    336-716-7782    dmcclain@wakehealth.edu   
Contact: Audrey Bell-Farrow, MBA, MHA    336-713-0370    abellfa@wakehealth.edu   
Sponsors and Collaborators
Wake Forest University Health Sciences
University of North Carolina, Chapel Hill
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Donald A McClain, MD, PhD Wake Forest University Health Sciences
More Information
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Publications:

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03696797    
Other Study ID Numbers: IRB00044393
1R01DK119913-01 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: September 28, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Iron Reduction
Phlebotomy
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