Impact of Liraglutide 3.0 on Body Fat Distribution, Visceral Adiposity, and Cardiometabolic Risk Markers In Overweight and Obese Adults at High Risk for Cardiovascular Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 235
- 试验地点
- 1
- 主要终点
- Relative Percent Reduction in Visceral Adipose Tissue Mass Measured by MRI
研究概览
简要总结
This study is a clinical study to investigate the efficacy of liraglutide compared to placebo in reducing visceral adiposity measured by MRI in overweight or obese subjects at high risk for cardiovascular disease after 40 weeks on-treatment.
详细描述
Obesity has long been recognized as a risk factor for all-cause mortality and morbidity, including the development of cardiovascular and metabolic diseases such as coronary artery disease, hypertension, insulin resistance, diabetes, and dyslipidemia. Obesity has recently been formally defined as a chronic disease characterized by pathophysiological processes that result in increased adipose tissue mass and can result in increased morbidity and mortality. Although the health risks associated with obesity are clear, there is an emerging appreciation that obesity per se, as defined by simple anthropometric measures such as waist circumference or body mass index (BMI), is neither necessary nor sufficient to promote cardiometabolic disease and atherosclerotic cardiovascular disease (ASCVD) risk. As a result, BMI alone is an insufficient marker of risk and may not accurately identify individuals at elevated risk for ASCVD. There is a pressing need to more accurately phenotype obesity to identify individuals at elevated risk for ASCVD that may benefit from more intensive preventive and therapeutic strategies
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 35 years
- •Able to provide informed consent
- •BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with metabolic syndrome
- •Metabolic syndrome is defined as at least three of the following:3
- •waist circumference > 102 cm (40 in) in men and 88 cm (35 in) in women
- •triglycerides > 150 mg/dL or on treatment for hypertriglyceridemia
- •HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women
- •blood pressure > 130/85 mmHg or on treatment for hypertension
- •fasting glucose > 100 mg/dL
排除标准
- •Treatment with Glucagon-like peptide-1 (GLP-1) receptor agonists (including liraglutide, exenatide or others as they become available), dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin within the last 3 months.
- •Receipt of any anti-obesity drug or supplement within 1 month prior to screening for this trial.
- •Self-reported or clinically documented history of significant fluctuations (>5% change) in weight within 3 months prior to screening for this trial.
- •History of diabetes mellitus (type 1 or 2) or on treatment with anti-diabetes medication.
- •History of chronic pancreatitis or idiopathic acute pancreatitis (current or prior history).
- •History of gallbladder disease (cholelithiasis or cholecystitis).
- •Chronic kidney disease stage III or greater (eGFR<60 mL/min).
- •Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome).
- •Current or history of treatment with medications that may cause significant weight gain, within 1 month prior to screening for this trial, including systemic corticosteroids (except for a short course of treatment, i.e., 7- 10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine, amitryptiline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium).
- •Diet attempts using herbal supplements or over-the-counter medications within 1 month prior to screening for this trial.
- •Current participation in an organized weight reduction program or within the last 1 month prior to screening for this trial.
- •Participation in a clinical trial within the last 3 months prior to screening for this trial.
- •Familial or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma.
- •Personal history of non-familial medullary thyroid carcinoma.
- •History of Major Depressive Disorder within the last 2 years.
- •History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder.
- •Any lifetime history of a suicide attempt.
- •A history of any suicidal behavior in the last month prior to randomization.
- •Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator.
- •Known or suspected hypersensitivity to trial product(s) or related product(s).
- •Known or suspected abuse of alcohol or narcotics.
- •Language barrier, mental incapacity, unwillingness or inability to understand.
- •Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. These include abstinence and the following methods: diaphragm with spermicide, condom with spermicide (by male partner), intrauterine device, sponge, spermicide, Norplant®, Depo-Provera® or oral contraceptives.
研究组 & 干预措施
Liraglutide 3.0 mg
Drug: Liraglutide Active Drug
Other Names:
- Saxenda
Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection.
干预措施: Liraglutide (Drug)
Placebo
Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL
Other Names:
- Placebo
- Saline injection
Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Relative Percent Reduction in Visceral Adipose Tissue Mass Measured by MRI
时间窗: Baseline, 40 weeks
The effect on relative percent reduction from baseline in visceral adipose tissue mass measured by MRI after 40 weeks on treatment. Positive numbers reflect the reduction in the value from baseline to study endpoint as a percent of the baseline. Reduction in this variable is believed to be associated with lower cardiovascular risk.
次要结局
- Relative Percent Reduction in Body Weight(Baseline, 40 weeks)
- Absolute Reduction in Visceral Adipose Tissue Volume(Baseline, 40 weeks)
- Relative Percent Reduction in Waist Circumference(Baseline, 40 weeks)
- Absolute Reduction in Body Weight(Baseline, 40 weeks)
- Absolute Reduction in Waist Circumference(Baseline, 40 weeks)
- Relative Percent Reduction in Total Body Adipose Tissue(Baseline, 40 weeks)
- Absolute Reduction in Total Body Adipose Tissue(Baseline, 40 weeks)
- Relative Percent Reduction in Abdominal Subcutaneous Adipose Tissue(Baseline, 40 weeks)
- Absolute Reduction in Abdominal Subcutaneous Adipose Tissue(Baseline, 40 weeks)
- Relative Percent Reduction in Lower Body Subcutaneous Adipose Tissue(Baseline, 40 weeks)
- Absolute Reduction in Lower Body Subcutaneous Adipose Tissue(Baseline, 40 weeks)
- Relative Percent Reduction in Liver Fat Percent(Baseline, 40 weeks)
- Absolute Reduction in Liver Fat Percent(Baseline, 40 weeks)
- Relative Percent Reduction in Total Body Lean Volume(Baseline, 40 weeks)
- Absolute Reduction in Total Body Lean Volume(Baseline, 40 weeks)
- Relative Percent Reduction in Total Thigh Muscle Volume(Baseline, 40 weeks)
- Absolute Reduction in Total Thigh Muscle Volume(Baseline, 40 weeks)
- Relative Percent Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent(Baseline,40 weeks)
- Absolute Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent(Baseline,40 weeks)
- Change From Baseline in VAT/SAT Ratio(Baseline, 40 weeks)
- Change From Baseline in Total Fat/Fat-free Mass Ratio(Baseline, 40 weeks)
- Relative Percent Change in Fasting Blood Glucose(Baseline, 40 weeks)
- Relative Percent Change in Insulin(Baseline, 40 weeks)
- Relative Percent Change in HOMA-IR(Baseline, 40 weeks)
- Relative Percent Change in C-reactive Protein(Baseline, 40 weeks)
- Relative Percent Change in Triglyceride/HDL-C Ratio(Baseline, 40 weeks)
- Relative Percent Change in Nt-proBNP(Baseline, 40 weeks)
- Absolute Change in Fasting Blood Glucose(Baseline,40 weeks)
- Absolute Change in Nt-proBNP(Baseline, 40 weeks)
- Change From Baseline in Heart Rate(Baseline, 40 weeks)
- Absolute Change in Insulin(Baseline, 40 weeks)
- Absolute Change in HOMA-IR(Baseline, 40 weeks)
- Absolute Change in CRP(Baseline, 40 weeks)
- Absolute Change in Triglyceride/HDL-C Ratio(Baseline, 40 weeks)
- Change From Baseline in Blood Pressure(Baseline, 40 weeks)
研究者
Parag Joshi
M.D.
University of Texas Southwestern Medical Center