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

March 26, 2025 updated by: Wake Forest University Health Sciences

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

68

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-2100
        • University of North Carolina at Chapel Hill (UNC)
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

36 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HgbA1C
Time Frame: Baseline, Month 6
Change in glycemia as measured byHgbA1C. Values from baseline and month 6 will be reported.
Baseline, Month 6
Change in ALT
Time Frame: Baseline, Month 12
ALT values from baseline and month 12 will be reported.
Baseline, Month 12
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.
Baseline, Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HgbA1C at Month 12
Time Frame: Month 12
HgbA1C values will be reported.
Month 12
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.
Month 6, Month 12
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.
Baseline, 12 months
Number of participants that Discontinued of oral antihyperglycemic agent
Time Frame: Month 12
The numbers of participants that discontinued of oral antihyperglycemic agents
Month 12
Change in Weight
Time Frame: Baseline, Month 12
The change in weight from baseline to month 12 will be reported
Baseline, Month 12
Change in Blood Pressure
Time Frame: Baseline, Month 12
The change in Blood pressure from baseline to month 12 will be reported
Baseline, Month 12
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.
Month 12
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.
Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of North Carolina, Chapel Hill

Investigators

  • Principal Investigator: Donald A McClain, MD, PhD, Wake Forest University Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 3, 2019

Primary Completion (Actual)

January 3, 2025

Study Completion (Actual)

January 3, 2025

Study Registration Dates

First Submitted

October 3, 2018

First Submitted That Met QC Criteria

October 3, 2018

First Posted (Actual)

October 5, 2018

Study Record Updates

Last Update Posted (Actual)

April 2, 2025

Last Update Submitted That Met QC Criteria

March 26, 2025

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00044393
  • 1R01DK119913-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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