Strategies for the Treatment of HIV Associated Metabolic Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Waist Circumference
研究概览
简要总结
A healthy diet and exercise have improved the health of people without human immunodeficiency virus (HIV) who have Metabolic Syndrome. In this study we would like to find out if the same benefit can be seen in people with HIV and Metabolic Syndrome. Patients with Metabolic Syndrome usually have a large waist, high blood cholesterol levels, high blood pressure, and high blood sugar levels. These are risk factors, which may increase one's chance of developing heart disease and/or diabetes. The purpose of the study is to evaluate the effects of different methods of treating HIV associated Metabolic Syndrome. The groups are: 1) a lifestyle modification program plus metformin (also known as glucophage), 2) lifestyle modification plus placebo, 3) metformin alone or 4) placebo alone. The lifestyle modification program consists of nutrition and exercise sessions with the goal of improving body composition, heart health, and ways to lower the risk of developing diabetes.
详细描述
After two initial screening visits with medical and nutrition staff for informed consent and determination of eligibility qualifying subjects will be seen for a baseline visit.
At baseline subjects will have an interval history and physical exam, lipodystrophy evaluation by investigator and patient report. Bloods will be taken for insulin, glucose, HgbA1c, lipid studies, creatinine, liver function, serum lactate, urine pregnancy (women), CD4, viral load, and complete blood count (CBC). Metabolic assessment will include a 2-hour oral glucose tolerance test and indirect calorimetry. Carotid ultrasound will be done for assessment of intima-media thickness. Body composition will be assessed by dual energy x-ray absorptiometry (DEXA), single-slice magnetic resonance imaging (MRI) scanning through the abdomen and mid thigh, magnetic resonance spectroscopy scanning to assess intramyocellular lipid of the calf, anthropometric measurements, and Cardiac computed tomography (CT) will be done.
After the baseline visit, subjects will be randomized to 1 of 4 groups: 1) a lifestyle modification program plus metformin (also known as glucophage), 2) lifestyle modification plus placebo, 3) metformin alone or 4) placebo alone.
The starting dose of metformin will be 500mg twice daily and this will increase to 850mg twice daily at the 3-month visit.
An identical visit to that at baseline will be repeated at 12-months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤ 65 years of age
- •HIV positive, on a stable combination antiretroviral regimen for > 6 months, including but not limited to either 2 nucleoside reverse transcriptase inhibitors (NRTI) and a non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitor (PI), or a triple NRTI regimen
- •Ability and motivation to modify behavior and make lifestyle changes
- •NCEP-Adult Treatment Panel III defined metabolic syndrome, as defined by 3 out of 5 of the following: 1) Waist circumference greater than 102 cm (40 in) in men and 88 cm (35 in) in women, 2) Triglycerides ≥ 150 mg/dL or current anti-lipolytic drug treatment, 3) high-density lipoprotein less than 40mg/dL in men and 50 mg/dL in women, 4) Blood pressure ≥ 130/85 mmHg or current antihypertensive drug treatment, 5) Fasting glucose ≥ 100 mg/dL
排除标准
- •Any new serious opportunistic infection within the past 6 weeks
- •History of unstable angina, aortic stenosis, uncontrolled hypertension, severe neuropathy, arthritis or other contraindication to exercise
- •Current therapy with insulin or other diabetic agent, fasting blood sugar > 126
- •Requiring parenteral nutrition or parenteral glucocorticoid therapy or oral glucocorticoid therapy
- •Estrogen, progestational derivative, or ketoconazole use within 3 months
- •New antiretroviral regimen in the past 6 months
- •Serum creatinine > 1.5 mg/dL (males) and 1.4 mg/dL (females), serum glutamic pyruvic transaminase-liver function (SGPT), > 2.5 upper limit of normal (ULN), Lactate > 2.0 ULN, hemoglobin < 10.0 mg/dL
- •Current substance and/or alcohol abuse
- •Known hypersensitivity to Metformin
- •Congestive heart failure requiring pharmacologic treatment
- •Use of cimetidine or planned use during the study period
- •Hypertrophic obstructive cardiomyopathy
- •Pregnant or actively seeking pregnancy, breastfeeding
- •Testosterone use for non-physiologic purposes, or physiologic testosterone replacement for < 3 months.
- •Presence of active AIDS including cancers
- •Current viral, bacterial or other infections (excluding HIV)
- •Weight loss in the past 3 months of greater than 10 pounds
- •Nitrates or other medications that can alter endothelial function
- •Contraindication to beta blocker or nitroglycerin use
- •Patients with previous allergic reactions to iodine-containing contrast media or to iodine
研究组 & 干预措施
Group 1
No Lifestyle Modification and Placebo
干预措施: Placebo (Drug)
Group 2
Lifestyle Modification and Placebo
干预措施: Placebo (Drug)
Group 2
Lifestyle Modification and Placebo
干预措施: Lifestyle Modification (Behavioral)
Group 3
No Lifestyle Modification and Metformin
干预措施: Metformin (Drug)
Group 4
Lifestyle Modification and Metformin
干预措施: Metformin (Drug)
Group 4
Lifestyle Modification and Metformin
干预措施: Lifestyle Modification (Behavioral)
结局指标
主要结局
Waist Circumference
时间窗: baseline and 12 months
Iliac waist circumference measurements were obtained using an inelastic tape measure. All measurements were obtained in triplicate, with the patient undressed, and then averaged. The change of the waist circumference measurement between baseline and 12 months is reported.
High Density Lipoprotein (HDL)
时间窗: baseline and 12 months
High density lipoprotein (HDL) was determined after an overnight fast. The change in HDL between baseline and 12 months is reported.
Glucose
时间窗: baseline and 12 months
Glucose level was determined after an overnight fast. The change in glucose between baseline and 12 months is reported.
Carotid Intima Media Thickness
时间窗: baseline and 12 months
Carotid intima media thickness imaging of the common carotid artery was conducted using a high-resolution 7.5-MHz phased-array transducer (SONOS 2000/2500. The change of the carotid intima media thickness measurement between baseline and 12 months is reported.
Systolic Blood Pressure
时间窗: baseline and 12 months
Systolic blood pressure was measured after 5 minutes rest. The in systolic blood pressure between baseline and 12 months is reported.
Coronary Artery Calcium Score
时间窗: baseline and 12 months
Computed tomography (CT) imaging was performed using a SOMATOM Sensation (Siemens Medical Solutions, Forcheim, Germany) 64-slice CT scanner. Agatston calcium score was calculated using CT images. The total Agatston score is calculated by summing up the scores of the individual calcifications in all slices of the CT scan. An absolute Agatston score of less than 10 indicates minimal overall atherosclerosis (plaques) in the coronary arteries. The change in the coronary artery calcium score between baseline and 12 months is reported.
次要结局
- Cardiorespiratory Fitness(baseline and 12 months)
- C-reactive Protein(baseline and 12 months)
- Intramyocellular Lipid(baseline and 12 months)
- Abdominal Visceral Adiposity(baseline and 12 months)
研究者
Steven K. Grinspoon, MD
Principal Investigator
Massachusetts General Hospital