Repurposing Colchicine to Improve Vascular Function in Hypertension
Кључне речи
Апстрактан
Опис
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.
Датуми
| Последња верификација: | 03/31/2020 |
| Фирст Субмиттед: | 01/22/2020 |
| Предвиђена пријава послата: | 03/09/2020 |
| Прво објављено: | 03/10/2020 |
| Послато последње ажурирање: | 04/26/2020 |
| Последње ажурирање објављено: | 04/27/2020 |
| Стварни датум почетка студије: | 05/14/2020 |
| Процењени датум примарног завршетка: | 03/31/2022 |
| Предвиђени датум завршетка студије: | 04/09/2023 |
Стање или болест
Интервенција / лечење
Drug: Colchicine
Drug: Placebo
Фаза
Групе руку
| Арм | Интервенција / лечење |
|---|---|
| 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 |
Критеријуми
| Узраст подобан за студирање | 40 Years До 40 Years |
| Полови подобни за студирање | Male |
| Прихвата здраве волонтере | да |
| Критеријуми | 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) |
Исход
Примарне мере исхода
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]
Секундарне мере исхода
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.]
