Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Myocardial Glucose Utilization Rate
研究概览
简要总结
We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. We hypothesize that exercise training or pioglitazone (Actos) will improve fat and sugar metabolism in the hearts of HIV+ people with The Metabolic Syndrome. This study will advance our understanding of cardiovascular disease in HIV+ people, and will test the efficacy of exercise training and pioglitazone for improving insulin resistance, heart metabolism and heart function in this at risk population.
详细描述
We hypothesize that myocardial free fatty acid and glucose utilization and oxidation rates are dysregulated in HIV+ people with The Metabolic Syndrome in comparison to HIV+ people without The Metabolic Syndrome, and in comparison to HIV-seronegative people with and without The Metabolic Syndrome. We hypothesize that dysregulated myocardial fatty acid and glucose metabolism is associated with impaired heart function (diastolic dysfunction) in HIV+ people with The Metabolic Syndrome. We will use myocardial positron emission tomography, radioactive isotope tracers of palmitate and glucose, and echocardiography to evaluate myocardial metabolism and function. HIV+ people with The Metabolic Syndrome will receive 16wks of exercise training or pioglitazone (Actos), and we will evaluate their potential beneficial effects on myocardial metabolism and function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 28 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All participants both with and without metabolic syndrome:
- •28-50 years old.
- •Plasma HIV RNA less than 5,000 copies/mL for previous 3 months OR CD4 count greater than 100 cells/µL for previous 3 months.
- •Stable for at least the past 3 months on any HAART regimen.
- •"Normal" blood chemistries for at least 1 month prior to enrollment: platelet count >50,000/mm3, absolute neutrophil count >750/mm3, liver transaminases <2.5x the upper limit of normal (ULN), creatinine <1.3x ULN, albumin >30g/L, creatine kinase <5.9x ULN.
- •Menstruating women must have a negative urine beta-HCG pregnancy test within 14 days prior to study. To control for potential metabolic effects of alterations in female hormones during the menstrual cycle, all menstruating women will be studied during the follicular phase (serum 17beta-estradiol <165 pg/mL).
排除标准
- •Frank obesity (BMI >35kg/m2).
- •Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.
- •Diabetes [fasting glucose >125 mg/dL, or fasting insulin >45 µU/mL, or 2-hr glucose >200mg/dL].
- •Medications or agents that regulate glucose metabolism (e.g., insulin-sensitizers, insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e. fibrate, statin).
- •Gestational diabetes, pregnancy, or nursing mothers.
- •Serum triglycerides ≥ 500 mg/dL.
- •Hypogonadism [total testosterone <200ng/dL (men) or <15ng/dL (women)]; thyroid disorder [TSH <0.2 or >12µIU/mL]; hypercortisolemia [morning cortisol >22µg/dL]. Replacement testosterone or thyroid hormones to normalize abnormal levels is acceptable, as long as treatment and blood levels have been stable for at least 3 months.
- •Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides) within the previous 3 months.
- •History of serious cardiovascular disease; MI, angina pectoris, heart failure, congenital heart disease, coronary artery disease, coronary artery bypass graft, stroke. Bundle branch block is exclusionary because it limits the interpretability of the resting/exercise ECG. Cardiovascular or physical contraindications to maximal exercise testing on a cycle ergometer.
- •Uncontrolled hypertension (>140/90 mmHg). Certain antihypertensive medications will be permitted (diuretics, ACE inhibitors) as long as the medication, dose, and blood pressure have been stable for at least 3 months.
- •Well-trained athletes (defined as >3 exercise training exposures/week; >30min regimented exercise/exposure maintained for at least the prior 4 weeks).
- •History of or active substance abuse (eg, alcoholism, cocaine, heroin, crack, methamphetamine, phencyclidine).
- •Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during 1 month prior to enrollment.
- •New serious systemic infection during the 3 weeks prior to enrollment.
- •History of hyperlactatemia or lactic acidosis, esp. with rapid weight loss.
- •Debilitating-painful myopathy or neuropathy that requires 'assistance' to conduct normal activities of daily living (dressing, hygiene, preparing meals, operating a vehicle). These might affect peripheral substrate metabolism.
- •Chronic renal insufficiency/failure or other comorbid conditions (eg. cancer, COPD) that alter metabolism.
- •Pancreatitis, celiac disease, or cirrhosis.
- •Inadequate macronutrient or energy intake, or malabsorptive disorder.
- •Dementia or any condition that would prevent voluntary informed consent or compliance.
- •Other compounds or blinded investigational new drugs that might affect metabolism or confound data interpretation (eg. RU486, interleukin therapy, or cytokine-receptor antagonist).
- •Oral glucocorticoid or corticosteroid use within previous 3 months.
研究组 & 干预措施
Pioglitazone
Pioglitazone (Actos, 30mg/day for 16 weeks)
干预措施: Pioglitazone (Drug)
Exercise Training
Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
干预措施: Exercise Training (Behavioral)
结局指标
主要结局
Myocardial Glucose Utilization Rate
时间窗: Weeks 0 and 16
Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate. The rate at which glucose exits the blood, enters the muscle cells in the left ventricle, and is metabolized (ATP generation, glycolysis, glycogenolysis, or lactate production). Total glucose utilization rate in the left ventricle of the heart.
Myocardial Glucose Utilization Rate Per Unit Insulin
时间窗: Weeks 0 and 16
Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate per unit of plasma insulin. Total glucose utilization rate in the left ventricle of the heart expressed per unit of the circulating plasma insulin concentration.
Myocardial Fatty Acid Utilization Rate
时间窗: Weeks 0 and 16
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid utilization rate. The rate at which palmitate exits the blood, enters the muscle cells in the left ventricle, and is metabolized (oxidation, re-esterification).
Myocardial Fatty Acid Oxidation Rate
时间窗: Weeks 0 and 16
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
Myocardial Fatty Acid Esterification
时间窗: Weeks 0 and 16
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction
次要结局
- Myocardial Contractile Function During Diastole(Weeks 0 and 16)
- Myocardial Contractile Function During Systole(Weeks 0 and 16)
- Fasting Lipids and Lipoproteins(Week 0 and 16)
- Fasting Glucose Insulin and HOMA(Week 0 and 16)
研究者
Kevin Yarasheski
Professor of Medicine
Washington University School of Medicine