Repurposing Colchicine to Improve Vascular Function in Hypertension
关键词
抽象
描述
In this project w the potential beneficial effect of the drug colchicine on vascular reactivity and blood pressure is evaluated. Colchicine is a commonly used anti-inflammatory medication approved for the treatment of gout, Familial Mediterranean Fever and pericarditis in Denmark. The current project idea is based on accumulating evidence in the literature for a beneficial role of colchicine treatment in the prevention of cardiovascular disease in parallel with novel mechanistic insight from research of the investigators. Recently, colchicine was associated with a lower risk of cardiovascular disease, including reduced myocardial infarctions, strokes and acute coronary syndrome. However, none of these trials have investigated the effect of colchicine on arterial tone or stiffness, changes to which may underlie the reduced risk of cardiovascular disease associated with colchicine. In support of thehypothesis that colchicine will improve vascular reactivity, a study in 1985 by Lagrue et al. found that daily, low-dose colchicine improved arterial stiffness in a small cohort of hypertensive patients. More recently, colchicine was shown to improve arterial stiffness in patients with Familial Mediterranean fever supporting a cardiovascular protective role of colchicine. Finally, colchicine is also proposed to have anti-inflammatory effects in the vascular system.
日期
| 最后验证: | 03/31/2020 |
| 首次提交: | 01/22/2020 |
| 提交的预估入学人数: | 03/09/2020 |
| 首次发布: | 03/10/2020 |
| 上次提交的更新: | 04/26/2020 |
| 最近更新发布: | 04/27/2020 |
| 实际学习开始日期: | 05/14/2020 |
| 预计主要完成日期: | 03/31/2022 |
| 预计完成日期: | 04/09/2023 |
状况或疾病
干预/治疗
Drug: Colchicine
Drug: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: Colchicine 3 weeks of treatment with colchicine | Drug: Colchicine patients with essential hypertension are randomized to receive either 3 weeks of colchicine |
| Placebo Comparator: Placebo 3 weeks of placebo-treatment | Drug: Placebo patients with essential hypertension are randomized to receive either 3 weeks of placebo-treatment |
资格标准
| 有资格学习的年龄 | 40 Years 至 40 Years |
| 有资格学习的性别 | Male |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Diagnosed with essential hypertension - BMI<30 - blood pressure (sys/dia) ≥120 mmhg and/or ≥80 mmhg while on hypertensive medication OR - blood pressure (sys/dia) ≥130 mmhg and/or ≥85 mmhg without hypertensive medication Exclusion Criteria: - smoking - excessive alcohol use - chronic diseases (beside essential hypertension) |
结果
主要结果指标
1. Changes in vascular function with treatment measured as flowchanges with ultrasound doppler in response to infusions of acetylcholine [Change in vascular conductance in response to infusions is assessed before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
2. Changes in vascular function with training measured as flowchanges with ultrasound doppler divided by changes in blood pressure measured with intraarterial canula, in response to infusions of isoprenaline [Change in vascular conductance in response to infusions is assessed before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
3. Changes in vascular function with training measured as flowchanges with ultrasound doppler divided by changes in blood pressure measured with intraarterial canula, in response to infusions of sodium nitroprusside [Change in vascular conductance in response to infusions is assessed before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
4. Changes in vascular function with training measured as flowchanges with ultrasound doppler divided by changes in blood pressure measured with intraarterial canula, in response to infusions of tyramine [Change in vascular conductance in response to infusions is assessed before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
5. Changes in arterial compliance measured with ultrasound doppler divided by changes in blood pressure measured with intraarterial canula, [Change in resting arterial compliance i is assessed before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
次要成果指标
1. Blood pressure [Measurements are made before and after 3 weeks of treatment with colchicine or placebo.]
2. Vascular compliance [Measurements are made before and after 3 weeks of treatment with colchicine or placebo.]
3. Vascular function [Measurements are made before and after 3 weeks of treatment with colchicine or placebo.]
