Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
研究概览
简要总结
The objective of this study is to determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.
详细描述
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.
There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.
Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.
Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.
The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers.
- •Patients taking oral hypoglycemic agents or insulin would be excluded.
- •Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures.
- •Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded.
- •People allergic to any of the class of drug such as lidocaine will also be excluded.
- •People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.
研究组 & 干预措施
Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
干预措施: metformin (Drug)
Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
干预措施: pioglitazone (Drug)
Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
时间窗: Baseline, 3 months
Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit \& was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp. The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates. The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute. The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan. Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
次要结局
- Change From Baseline in Fasting Blood Glucose Level(Baseline, 3 months)
- Change From Baseline in Glycosylated Hemoglobin (HbA1c)(Baseline, 3 months)
- Change From Baseline in Insulin Levels(Baseline, 3 months)
- Change From Baseline in Lipid Profile(Baseline, 3 months)
- Change From Baseline in the Thrombotic Biomarker Fibrinogen(Baseline, 3 months)
- Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)(Baseline, 3 months)
- Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)(Baseline, 3 months)
- Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)(Baseline, 3 months)
- Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)(Baseline, 3 month)
- Change From Baseline in the Inflammatory Biomarker Adiponectin(Baseline, 3 months)
研究者
K. Sreekumaran Nair
Professor of Medicine
Mayo Clinic