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

Primary Purpose

Iron, Diabetes, Nonalcoholic Fatty Liver

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Blood Donation
Sham Blood Donation
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron focused on measuring Iron Reduction, Phlebotomy

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina at Chapel Hill (UNC)Recruiting
  • Wake Forest University Health SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Treatment Group

Control Group

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

HgbA1C at Month 12
HgbA1C values will be reported.
Change in fasting glucose
Fasting glucose measured on glucose machine (Abbott Freestyle Libre Pro system). Values of month 6 and month 12 will be reported.
Change in HOMA-IR (Homeostatic Model Assessment-Insulin Resistance)
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.
Number of participants that Discontinued of oral antihyperglycemic agent
The numbers of participants that discontinued of oral antihyperglycemic agents
Change in Weight
The change in weight from baseline to month 12 will be reported
Change in Blood Pressure
The change in Blood pressure from baseline to month 12 will be reported
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.
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.

Full Information

First Posted
October 3, 2018
Last Updated
August 25, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
University of North Carolina, Chapel Hill, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03696797
Brief Title
Iron Reduction for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease
Official Title
Iron Reduction by Phlebotomy for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
University of North Carolina, Chapel Hill, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron, Diabetes, Nonalcoholic Fatty Liver
Keywords
Iron Reduction, Phlebotomy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
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.
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Group
Arm Type
Active Comparator
Arm Description
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
Arm Title
Control Group
Arm Type
Sham Comparator
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Blood Donation
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Sham Blood Donation
Intervention Description
Participants will have a needle inserted their arm, however, no blood will be drawn.
Primary Outcome Measure Information:
Title
Change in HgbA1C
Description
Change in glycemia as measured byHgbA1C. Values from baseline and month 6 will be reported.
Time Frame
Baseline, Month 6
Title
Change in ALT
Description
ALT values from baseline and month 12 will be reported.
Time Frame
Baseline, Month 12
Title
Change in FSIGTT DI (Frequently sampled intravenous glucose tolerance test)
Description
FSIGTT DI Values from baseline and month 6 will be reported.
Time Frame
Baseline, Month 6
Secondary Outcome Measure Information:
Title
HgbA1C at Month 12
Description
HgbA1C values will be reported.
Time Frame
Month 12
Title
Change in fasting glucose
Description
Fasting glucose measured on glucose machine (Abbott Freestyle Libre Pro system). Values of month 6 and month 12 will be reported.
Time Frame
Month 6, Month 12
Title
Change in HOMA-IR (Homeostatic Model Assessment-Insulin Resistance)
Description
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.
Time Frame
Baseline, 12 months
Title
Number of participants that Discontinued of oral antihyperglycemic agent
Description
The numbers of participants that discontinued of oral antihyperglycemic agents
Time Frame
Month 12
Title
Change in Weight
Description
The change in weight from baseline to month 12 will be reported
Time Frame
Baseline, Month 12
Title
Change in Blood Pressure
Description
The change in Blood pressure from baseline to month 12 will be reported
Time Frame
Baseline, Month 12
Title
Number of participants that converted from pre-diabetes to Diabetes
Description
Number of participants that converted from pre-Diabetes to Diabetes based on the HbA1C criteria.
Time Frame
Month 12
Title
Number of participants that converted from pre-diabetes to normal glucose tolerance
Description
Number of participants that converted from pre-Diabetes to normal glucose tolerance based on the HbA1C criteria.
Time Frame
Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Donald A McClain, MD, Ph.D
Phone
336-716-7782
Email
dmcclain@wakehealth.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Audrey Bell-Farrow, MBA, MHA
Phone
336-713-0370
Email
abellfa@wakehealth.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald A McClain, MD, PhD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill (UNC)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-2100
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Buse, MD, Ph.D
Phone
919-966-0134
Email
John_buse@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Laura Young, MD
Phone
(919) 966-3465
Email
Laura_Young@med.unc.edu
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donald A McClain, MD
Phone
336-716-7782
Email
dmcclain@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Audrey Bell-Farrow, MBA, MHA
Phone
336-713-0370
Email
abellfa@wakehealth.edu

12. IPD Sharing Statement

Plan to Share IPD
No
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PubMed Identifier
11978935
Citation
Beutler E, Felitti V, Ho NJ, Gelbart T. Relationship of body iron stores to levels of serum ferritin, serum iron, unsaturated iron binding capacity and transferrin saturation in patients with iron storage disease. Acta Haematol. 2002;107(3):145-9. doi: 10.1159/000057632.
Results Reference
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Iron Reduction for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease

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