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

Not Applicable

Active, not recruiting

• Conditions: Iron; Nonalcoholic Fatty Liver; Diabetes
• Interventions: Procedure: Sham Blood Donation; Procedure: Blood Donation

• Registration Number: NCT03696797
• Lead Sponsor: Wake Forest University Health Sciences

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.

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 Timeline

• Study First Submitted: 2018-10-03
• Study First Submitted QC: 2018-10-03
• Study First Posted: 2018-10-05
• Study Start: 2019-05-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-26
• Last Update Posted: 2024-07-30
• Primary Completion: 2025-02-01
• Study Completion: 2025-02-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 68

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Sham Blood Donation	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
Treatment Group	Blood Donation	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

Primary Outcome Measures

Name	Time	Method
Change in HgbA1C	Baseline, Month 6	Change in glycemia as measured byHgbA1C. Values from baseline and month 6 will be reported.
Change in FSIGTT DI (Frequently sampled intravenous glucose tolerance test)	Baseline, Month 6	FSIGTT DI Values from baseline and month 6 will be reported.
Change in ALT	Baseline, Month 12	ALT values from baseline and month 12 will be reported.

Secondary Outcome Measures

Name	Time	Method
Change in fasting glucose	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.
HgbA1C at Month 12	Month 12	HgbA1C values will be reported.
Number of participants that converted from pre-diabetes to normal glucose tolerance	Month 12	Number of participants that converted from pre-Diabetes to normal glucose tolerance based on the HbA1C criteria.
Number of participants that Discontinued of oral antihyperglycemic agent	Month 12	The numbers of participants that discontinued of oral antihyperglycemic agents
Number of participants that converted from pre-diabetes to Diabetes	Month 12	Number of participants that converted from pre-Diabetes to Diabetes based on the HbA1C criteria.
Change in HOMA-IR (Homeostatic Model Assessment-Insulin Resistance)	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.
Change in Weight	Baseline, Month 12	The change in weight from baseline to month 12 will be reported
Change in Blood Pressure	Baseline, Month 12	The change in Blood pressure from baseline to month 12 will be reported

Trial Locations

Locations (2)

University of North Carolina at Chapel Hill (UNC); 🇺🇸 Chapel Hill, North Carolina, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States