Effect of PDE5 Inhibition on Adipose Metabolism in Humans
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Thermoneutral FSF of WAT at the level of the umbilicus at 12 Weeks.
研究概览
简要总结
This is a randomized, double-blinded, placebo-controlled study of the effects of PDE5 inhibition with tadalafil on adipose tissue in obese individuals. Adipose metabolism will be measured using magnetic resonance imaging (MRI) scans and by aspirating a small amount of adipose to measure gene expression.
详细描述
The purpose of this study is to test whether tadalafil causes subcutaneous adipose tissue to have a "beige" phenotype. Participants will be randomized to either placebo or tadalafil for 12 weeks. Investigators will study adipose metabolism using MRI scans and aspiration of subcutaneous adipose from the abdomen. In addition to MRI scans at room temperature, the investigators will use a cooling protocol to test the combined effects of tadalafil and on adipose metabolism. Investigators will also measure the effects of the drug on body composition. In addition to the study visits, participants will wear an activity tracker (Fitbit) and log their dietary intake several times using an online tool. There will be a small amount of radiation exposure. Participants will be compensated for participation in this study.
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, Investigator)
盲法说明
Double blinded
入排标准
- 年龄范围
- 19 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Obesity (BMI ≥ 30 kg/m2)
排除标准
- •Age <19 or > 50
- •BMI < 30 kg/m2
- •Systolic blood pressure (SBP) < 100, > 150 mmHg
- •Current anti-hypertensive medication use, including diuretics
- •Current use of organic nitrates
- •Current use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil)
- •History of reaction to PDE-5 inhibitors
- •Known HIV infection
- •Use of medications that strongly alter CYP3A4 activity
- •History of myocardial infarction, angina, uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, or seizure
- •Known non-arteritic ischemic optic retinopathy (NAIOR)
- •History of hearing loss
- •Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 by the modified diet in renal disease (MDRD) equation
- •Hepatic transaminase (AST and ALT) levels greater than three times the upper limit of normal
- •Known pregnancy or breastfeeding or those unwilling to avoid pregnancy during the course of the study
- •History of priapism
- •Use in excess of four alcoholic drinks daily
- •History of diabetes mellitus or use of anti-diabetic medications
- •Known anemia (men, Hct < 38% and women, Hct <36%)
- •Menopause
- •Weight > 300 pounds
- •Individuals with circadian rhythm disorders, shift workers, or those who travel across time zones frequently
研究组 & 干预措施
Placebo
Subjects will be randomized to one of two arms. 50 obese adult subjects will be randomized to the placebo arm following the screening visit. Beginning at their baseline visit, they will receive an oral daily dose of a placebo pill (20mg) that they will take for 12 weeks (through their completion of the study). After randomization has occurred, the placebo comparator subjects will undergo the following visit protocol: screening visit, baseline, an interim visit (10 weeks post-baseline), and a 12-week visit.
干预措施: Placebo (Drug)
Tadalafil
Subjects will be randomized to one of two arms. 50 obese adult subjects will be randomized to the Tadalafil arm following the screening visit. Beginning at their baseline visit, they will receive an oral daily dose of Tadalafil (20mg) that they will take for 12 weeks (through their completion of the study). After randomization has occurred, the active comparator subjects will undergo the following visit protocol: screening visit, baseline visit, an interim visit (10 weeks post-baseline), and a 12-week visit.
干预措施: Tadalafil 20 MG (Drug)
结局指标
主要结局
Thermoneutral FSF of WAT at the level of the umbilicus at 12 Weeks.
时间窗: 12 weeks
MRI measurement of lipid content
Subcutaneous adipose tissue expression of UCP1 (normalized expression units)
时间窗: 12 weeks
Measurement of gene expression in adipose sample
Thermoneutral FSF of WAT at the Level of the Umbilicus at 12 Weeks.
时间窗: 12 weeks
Measured by fat signal fraction (FSF) at Week 12. FSF is the percent of MRI signal derived from lipids within a voxel. Lower FSF values indicate greater lipid consumption and correspond to brown adipose tissue (BAT), whereas higher FSF values indicate lipid storage and correspond to white adipose tissue (WAT).
Thermoneutral Subcutaneous Adipose Tissue Expression of UCP1 (Normalized Expression Units) at 12 Weeks.
时间窗: 12 weeks
Measured by mRNA expression of subcutaneous adipose tissue obtained via biopsy at 12 weeks. Higher expression of UCP1 indicates increased thermogenic (beige/brown) adipose activity; lower expression indicates a white adipose phenotype associated with reduced energy expenditure.
次要结局
- Subcutaneous adipose tissue natriuretic peptide receptor expression(Baseline to 12 weeks)
- Thermoneutral fat signal fraction of brown adipose tissue(Baseline to 12 weeks)
- Cold-exposed fat signal fraction of white adipose tissue and grown adipose tissue(Baseline to 12 weeks)
- Subcutaneous adipose tissue gene expression of mitochondrial genes (normalized expression units)(Baseline to 12 weeks)
研究者
Evan Brittain
Professor of Medicine
Vanderbilt University Medical Center