Effects on Insulin Resistance With the Phosphodiesterase-5 Inhibitor Tadalafil in Type 2 Diabetes - a Double-blind, Placebo-controlled Crossover Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- insulin sensitivity
研究概览
简要总结
The aim is to continue our program on PDE5 inhibition by evaluating effects on insulin resistance, including glucose metabolism and subclinical inflammation, after a 6-week administration of tadalafil in T2D patients. The primary objective is to study the effect of tadalafil compared with placebo on insulin sensitivity during a euglycemic hyperinsulinemic clamp.
This is a double-blind, placebo-controlled crossover study with one study site. Twenty-five T2D patients will be recruited and randomized to per oral intake of tadalafil 20 mg o.d. for six weeks and after a wash-out period of eight weeks intake of placebo for another six weeks, or vice versa. At the end of each 6 week treatment period a glucose clamp, subcutaneous needle biopsies as well as muscle and subcutaneous microdialysis will be performed. Endothelial function tests and arginin stimulation of insulin secretion tests will be performed after 3 weeks in each treatment arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •T2D patient, previously diagnosed by fasting or 2-hr OGTT plasma glucose levels
- •Age females: 55-70 yrs (post-menopausal state defined as natural amenorrhea for at least 12 months); Age males: 40-70 yrs
- •BMI: 27-40 kg/m2
- •HbA1c < 60 mmol/mol
- •Type 2 diabetes duration > 3 months and < 10 yrs
- •Understand and speak Swedish
排除标准
- •Diabetes treatment with glitazones, GLP-1 analogues or DPP-IV inhibitors
- •Anti-hypertensive therapy with beta-blockers, ACE-inhibitors and/or angiotensin-II receptor blockers
- •Significant microvascular complications e.g. nephropathy (GFR<60), proliferative retinopathy and symptomatic neuropathy e.g. postural hypotension
- •Previous significant vascular disease including angina pectoris and myocardial infarction, cerebral artery disease e.g. history of transient ischemic attacks and peripheral artery disease with no palpable pulses
- •Smoking > 10 cig/day and/or smokeless tobacco > one can per 2 days
- •Concurrent use of nitrates or NO donors, or an apparent risk that there may be a need of such medication
- •Cardiac failure (stages NYHA II-IV)
- •Uncontrolled hypertension > 170/105 mm Hg
- •Apparent ECG-pathology indicating current or previous myocardial ischemia;
- •Males with erectile dysfunction
- •Hemophilia or a history of bruises or hepatic failure (> 2-fold increase upper limit normal values of ASAT/ALAT)
- •Hypotension
- •Treatment with doxazosin
- •Anything in the contact with the patient that makes the doctor to believe that he/she will be uncompliant to the protocol.
研究组 & 干预措施
Tadalafil
Per oral intake of tadalafil 20 mg o.d. for six weeks
干预措施: Tadalafil (Drug)
Placebo
Per oral intake of placebo
干预措施: Placebo (Drug)
结局指标
主要结局
insulin sensitivity
时间窗: 6 week treatment with drug or placebo
To evaluate the effect (difference in glucose disposal rate (mg/kg/min)) of daily administration of 20 mg tadalafil for 6 weeks ("chronic" treatment) on insulin sensitivity in muscle by assessing glucose disposal rate during a 3-hour euglycemic hyperinsulinemic glucose clamp (120 mU/m2/min) in T2D patients
次要结局
- Mean glucose (HbA1c, mmol/mol) in blood(Up to 6 weeks after start of treatment.)
- Fasting plasma glucose levels (mmol/l)(Up to 6 weeks after start of treatment.)
- Arginine-induced insulin secretion (area under curve, AUC, mU/l/min) in blood(3 weeks after start of treatment.)
- Levels interstitial insulin(Up to 6 weeks after start of treatment.)
- Lactate concentrations in insulin sensitive tissues(Up to 6 weeks after start of treatment.)
- Levels of inflammatory markers in blood(Up to 6 weeks after start of treatment.)
- Endothelial function in peripheral arteries measured with EndoPAT, measured as difference in reactive hyperemia(3 weeks after start of treatment.)