Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia
研究概览
简要总结
Rationale:
Statins form a class of drugs that is widely prescribed for hypercholesterolaemia, specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the effect for which the drug was originally developed, it became obvious that statins have several other beneficial effects. Such pleiotropic effects include the activation of ecto-5'-nucleotidase which can increase endogenous adenosine production (by dephosphorylation adenosine monophosphate into adenosine) and subsequently cause vasodilation. A recent study of Meijer et al (not yet published) showed that rosuvastatin significantly augments vasodilation after a brief period of ischemia (post occlusive reactive hyperaemia). However, it is not yet verified whether this increase in post occlusive reactive hyperaemia is truly caused by a rise of extracellular adenosine and subsequent adenosine receptor stimulation. In this study, the mechanism by which rosuvastatin augments post occlusive reactive hyperaemia will be investigated by blocking adenosine receptors with caffeine, a competitive A1 and A2 adenosine receptor antagonist. Caffeine is a substance that can be safely used in normal concentrations to block the adenosine receptor.
Hypothesis:
The augmenting effect of rosuvastatin on PORH is caused by an increase of extracellular adenosine formation and this effect can be diminished by blocking the adenosine receptor using caffeine.
Objective:
To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7 days treatment with rosuvastatin.
Study design:
Open label cross-over design Study population: Healthy volunteers, 18-50 years of age
Intervention:
Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily before and after rosuvastatin treatment caffeine will be administrated intra-arterially.
Main study parameters/endpoints:
Forearm blood flow (FBF) will be measured as an indicator for post occlusive reactive hyperaemia (PORH).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-50
- •Written informed consent
排除标准
- •History of any cardiovascular disease
- •Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
- •Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
- •Hyperlipidemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
- •Alanine amino transferase >90 U/L
- •Creatin kinase >440 U/L
- •Raised rhabdomyolysis risk (GFR <80 ml/min and/or overt clinical signs of hypothyroidism and/or myopathy in family history
- •Alcohol abuse
- •Concommitant chronic use of medication
- •Participation to any drug-investigation during the previous 60 days as checked with VIP check
研究组 & 干预措施
2
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm
干预措施: caffeine (Drug)
3
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg
干预措施: rosuvastatin (Drug)
4
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm
干预措施: rosuvastatin (Drug)
4
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm
干预措施: caffeine (Drug)
结局指标
主要结局
Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia
时间窗: before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine
次要结局
未报告次要终点