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IronNCT03696797

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

A study testing Blood Donation in people with Iron and Diabetes, run by Wake Forest University Health Sciences at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 75 years
Conditions the study is for
Iron, Diabetes, Nonalcoholic Fatty Liver
What is being tested?
Blood Donation
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
132 participants
Where
2 sitesUnited States
Study dates
3 May 2019to 3 Jan 2025
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • University of North Carolina at Chapel Hill (UNC)

    Chapel Hill, North Carolina, 27599-2100

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: 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.

Read the 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).

Being tested
Blood Donation, Sham Blood Donation
Keywords
Iron Reduction, Phlebotomy
Medical subject headings
Diabetes Mellitus, Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood DonationProcedure or surgery

    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 Blood DonationProcedure or surgery

    Participants will have a needle inserted their arm, however, no blood will be drawn.

Study groups in NCT03696797
Study groupRoleWhat they receive
Treatment GroupActive comparatorWill 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
Receives: Procedure: Blood Donation
Control GroupSham comparatorWill 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
Receives: Procedure: Sham Blood Donation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HgbA1c Value

    HgbA1c measures average blood glucose levels over the past 2-3 months. HgbA1C values from baseline and month 6 will be reported.

    Measured: Baseline

  2. HgbA1c Value

    HgbA1c measures average blood glucose levels over the past 2-3 months. HgbA1C values from baseline and month 6 will be reported.

    Measured: month 6

  3. ALT (Alanine Aminotransferase) Value

    An ALT test measures a liver enzyme. ALT values from baseline and month 12 will be reported.

    Measured: Baseline

  4. ALT Value

    An ALT test measures a liver enzyme. ALT values from baseline and month 12 will be reported.

    Measured: month 12

  5. FSIGTT DI (Frequently Sampled Intravenous Glucose Tolerance Test) Value

    Studies often report DI values with a wide range. Normal or reference ranges can vary substantially depending on the study. Higher values indicate better -cell function. The Disposition Index (DI) derived from the Frequently Sampled Intravenous Glucose Tolerance Test (FSIGTT) is a measure of pancreatic -cell function, calculated as the product of insulin sensitivity (S1) and the acute insulin response to glucose (AIRg). It acts as a marker for how well insulin secretion compensates for insulin.

    Measured: Baseline

  6. FSIGTT DI Value

    Studies often report DI values with a wide range. Normal or reference ranges can vary substantially depending on the study. Higher values indicate better -cell function. The Disposition Index (DI) derived from the Frequently Sampled Intravenous Glucose Tolerance Test (FSIGTT) is a measure of pancreatic -cell function, calculated as the product of insulin sensitivity (S1) and the acute insulin response to glucose (AIRg). It acts as a marker for how well insulin secretion compensates for insulin.

    Measured: month 6

Secondary outcomes (8)
  1. HgbA1c Value at Month 12

    HgbA1c measures average blood glucose levels over the past 2-3 months.

    Measured: Month 12

  2. Change in Fasting Glucose

    Fasting glucose measured on glucose machine (Abbott Freestyle Libre Pro system). Difference in values from baseline through month 6 and baseline through month 12 will be reported.

    Measured: Month 6, Month 12

  3. HOMA-IR (Homeostatic Model Assessment-Insulin Resistance) Score

    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. HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a calculated score that uses fasting insulin and glucose to measure insulin resistance. An optimal score is generally below 1.0, while values above 1.9 suggest early insulin resistance, and those above 2.9 indicate significant insulin resistance. HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) measures insulin resistance by multiplying fasting insulin and fasting glucose, then dividing by 405. A score below 1.0 indicates optimal insulin sensitivity, while above 1.9-2.0 suggests early resistance, and above 2.9 indicates significant resistance.

    Measured: baseline, month 12

  4. Number of Participants That Discontinued of Oral Antihyperglycemic Agent

    The numbers of participants that discontinued of oral antihyperglycemic agents

    Measured: Month 12

  5. Change in Weight

    The change in weight from baseline to month 12 will be reported

    Measured: Baseline, Month 12

  6. Change in Systolic Blood Pressure

    The change in systolic Blood pressure from baseline to month 12 will be reported

    Measured: Baseline, Month 12

  7. Number of Participants That Converted From Pre-diabetes to Diabetes

    Number of participants that converted from pre-Diabetes to Diabetes based on the HbA1C criteria.

    Measured: Month 12

  8. Number of Participants That Converted From Pre-diabetes to Normal Glucose Tolerance

    Number of participants that converted from pre-Diabetes to normal glucose tolerance based on the HbA1C criteria.

    Measured: Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2018
  2. Study start3 May 2019
  3. Primary completion3 Jan 2025
  4. Study completion3 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03696797
Sponsor's protocol ID
IRB00044393
Other IDs
1R01DK119913-01
Status last verified
Jul 2024
First submitted
3 Oct 2018
Last updated
9 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Buysschaert M, Paris I, Selvais P, Hermans MP. Clinical aspects of diabetes secondary to idiopathic haemochromatosis in French-speaking Belgium. Diabetes Metab. 1997 Sep;23(4):308-13.

    PubMed 9342544
  • Abraham D, Rogers J, Gault P, Kushner JP, McClain DA. Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis. Diabetologia. 2006 Nov;49(11):2546-51. doi: 10.1007/s00125-006-0445-7. Epub 2006 Sep 22.

    PubMed 17019598
  • Bulaj ZJ, Ajioka RS, Phillips JD, LaSalle BA, Jorde LB, Griffen LM, Edwards CQ, Kushner JP. Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med. 2000 Nov 23;343(21):1529-35. doi: 10.1056/NEJM200011233432104.

    PubMed 11087882
  • Dmochowski K, Finegood DT, Francombe W, Tyler B, Zinman B. Factors determining glucose tolerance in patients with thalassemia major. J Clin Endocrinol Metab. 1993 Aug;77(2):478-83. doi: 10.1210/jcem.77.2.8345055.

    PubMed 8345055
  • Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care. 1999 Dec;22(12):1978-83. doi: 10.2337/diacare.22.12.1978.

    PubMed 10587829
  • Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004 Feb 11;291(6):711-7. doi: 10.1001/jama.291.6.711.

    PubMed 14871914
  • Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr. 2002 Dec;76(6):1375-84. doi: 10.1093/ajcn/76.6.1375.

    PubMed 12450906
  • Afkhami-Ardekani M, Rashidi M. Iron status in women with and without gestational diabetes mellitus. J Diabetes Complications. 2009 May-Jun;23(3):194-8. doi: 10.1016/j.jdiacomp.2007.11.006. Epub 2008 Apr 16.

    PubMed 18413178
  • Wilson JG, Lindquist JH, Grambow SC, Crook ED, Maher JF. Potential role of increased iron stores in diabetes. Am J Med Sci. 2003 Jun;325(6):332-9. doi: 10.1097/00000441-200306000-00004.

    PubMed 12811229
  • Qiu C, Zhang C, Gelaye B, Enquobahrie DA, Frederick IO, Williams MA. Gestational diabetes mellitus in relation to maternal dietary heme iron and nonheme iron intake. Diabetes Care. 2011 Jul;34(7):1564-9. doi: 10.2337/dc11-0135.

    PubMed 21709295
  • Bowers K, Yeung E, Williams MA, Qi L, Tobias DK, Hu FB, Zhang C. A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus. Diabetes Care. 2011 Jul;34(7):1557-63. doi: 10.2337/dc11-0134.

    PubMed 21709294
  • Sharifi F, Nasab NM, Zadeh HJ. Elevated serum ferritin concentrations in prediabetic subjects. Diab Vasc Dis Res. 2008 Mar;5(1):15-8. doi: 10.3132/dvdr.2008.003.

    PubMed 18398807
  • Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care. 2004 Oct;27(10):2422-8. doi: 10.2337/diacare.27.10.2422.

    PubMed 15451911
  • Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, Taioli E, Valenti L, Fiorelli G. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol. 2001 Aug;96(8):2448-55. doi: 10.1111/j.1572-0241.2001.04052.x.

    PubMed 11513189
  • Altamura S, Muckenthaler MU. Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J Alzheimers Dis. 2009;16(4):879-95. doi: 10.3233/JAD-2009-1010.

    PubMed 19387120

Questions about this trial

What is this clinical trial studying?

A study testing Blood Donation in people with Iron and Diabetes, run by Wake Forest University Health Sciences at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HgbA1c Value (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03696797, which also lists 40 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.

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