The Effect of Lipid Lowering by Acipimox on Cardiac and Skeletal Muscle Mitochondrial Function
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- changes in mitochondrial function
研究概览
简要总结
Accumulation of lipid in skeletal and cardiac muscle has been associated with insulin resistance and diabetic cardiomyopathy. In skeletal muscle, lipotoxic damage has been suggested to lead to dysfunction of mitochondria. It remains unknown whether lipotoxicity leads to mitochondrial dysfunction in heart as well, and if so, whether this also leads to cardiomyopathy (failure of the heart). Although it has been shown that lipid lowering agents can improve insulin sensitivity, the effect of lowering free fatty acids on cardiac and skeletal muscle mitochondrial function remains unknown. In this study the investigators want to investigate whether lowering cardiac and muscular lipid content will improve mitochondrial and cellular function in type 2 diabetic patients.
To this end, type 2 diabetic patients and body mass index (BMI)-matched controls will be included in a blinded cross-over design, in which subjects will receive a lipid lowering agent (Acipimox) or placebo for 2 weeks in random order. During treatment, diabetes medication will be stopped. Baseline measurements will be performed prior to the study and after each treatment to assess cardiac and muscular lipid accumulation, cardiac function, mitochondrial function and insulin sensitivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- 是
入选标准
- •Male or postmenopausal females
- •Age 40-70 years
- •Obese (BMI > 30 kg/m2), non-insulin dependent type 2 diabetic patients and BMI matched control subjects without diabetes.
- •Generally healthy with specifically no known cardiovascular disease, dyslipidemia, or gastric ulcers (contra-ind. of Acipimox), which can affect the study parameters.
- •Must be on sulphonylurea(SU)- derivate or metformin therapy for at least six months with a constant dose for at least two months, or on dietary treatment for at least six months
- •Well-controlled diabetes: HbA1c<8%.
- •Control subjects must have a plasma glucose lower than 6,1 mmol/L.
- •Stable dietary habits (no weight loss/gain > 3 kg in the last 6 months)
排除标准
- •Known cardiovascular disease, dyslipidemia, hepatic or renal failure and gastric ulcers.
- •Insulin dependent Diabetic patients.
- •Use of lipid lowering agents, except from Statins, as these do not affect triglycerides levels (with exception to Lipitor).
- •Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
- •Use of anti-coagulants (not thrombocyte-aggregation inhibitors)
- •Aberrant ECG (with signs of ischemia or cardiac failure or arrythmia's)
- •Weight gain/loss > 3 kg in the last 6 months.
- •Hb < 7,3 in women, and < 7,8 in men.
- •Contraindications for MRI scans:
- •Electronic implants such as pacemakers or neurostimulator
- •Iron-containing corpora aliena in eyes or brain
- •Some hearing aids and artificial (heart) valves which are contraindicated for MRS
- •Claustrophobia
- •Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their physician is informed, cannot participate in the study.
研究组 & 干预措施
Acipimox
Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.
干预措施: Acipimox (Drug)
Cellulosum mycrocryst capsula
Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.
干预措施: Cellulosum Mycrocryst (Drug)
结局指标
主要结局
changes in mitochondrial function
时间窗: 2 weeks
changes in cardiac function
时间窗: 2 weeks
lipid accumulation in ectopic tissue (cardiac and skeletal muscle)
时间窗: 2 weeks
次要结局
- oxidative stress markers(2 weeks)
- insulin sensitivity(2 weeks)