Iron Reduction by Phlebotomy for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 2
- 主要终点
- HgbA1c Value
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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
干预措施: Blood Donation (Procedure)
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
干预措施: Sham Blood Donation (Procedure)
结局指标
主要结局
HgbA1c Value
时间窗: Baseline
HgbA1c measures average blood glucose levels over the past 2-3 months. HgbA1C values from baseline and month 6 will be reported.
HgbA1c Value
时间窗: month 6
HgbA1c measures average blood glucose levels over the past 2-3 months. HgbA1C values from baseline and month 6 will be reported.
ALT (Alanine Aminotransferase) Value
时间窗: Baseline
An ALT test measures a liver enzyme. ALT values from baseline and month 12 will be reported.
ALT Value
时间窗: month 12
An ALT test measures a liver enzyme. ALT values from baseline and month 12 will be reported.
FSIGTT DI (Frequently Sampled Intravenous Glucose Tolerance Test) Value
时间窗: Baseline
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.
FSIGTT DI Value
时间窗: month 6
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.
次要结局
- Change in Weight(Baseline, Month 12)
- HgbA1c Value at Month 12(Month 12)
- Change in Fasting Glucose(Month 6, Month 12)
- HOMA-IR (Homeostatic Model Assessment-Insulin Resistance) Score(baseline, month 12)
- Number of Participants That Discontinued of Oral Antihyperglycemic Agent(Month 12)
- Change in Systolic Blood Pressure(Baseline, Month 12)
- Number of Participants That Converted From Pre-diabetes to Diabetes(Month 12)
- Number of Participants That Converted From Pre-diabetes to Normal Glucose Tolerance(Month 12)