Repurposing Colchicine to Improve Vascular Function in Hypertension
Klíčová slova
Abstraktní
Popis
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.
Termíny
| Poslední ověření: | 03/31/2020 |
| První předloženo: | 01/22/2020 |
| Odhadovaná registrace vložena: | 03/09/2020 |
| První zveřejnění: | 03/10/2020 |
| Poslední aktualizace byla odeslána: | 04/26/2020 |
| Poslední aktualizace zveřejněna: | 04/27/2020 |
| Aktuální datum zahájení studie: | 05/14/2020 |
| Odhadované datum dokončení primární: | 03/31/2022 |
| Odhadované datum dokončení studie: | 04/09/2023 |
Stav nebo nemoc
Intervence / léčba
Drug: Colchicine
Drug: Placebo
Fáze
Skupiny zbraní
| Paže | Intervence / léčba |
|---|---|
| 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 |
Kritéria způsobilosti
| Věky způsobilé ke studiu | 40 Years Na 40 Years |
| Pohlaví způsobilá ke studiu | Male |
| Přijímá zdravé dobrovolníky | Ano |
| Kritéria | 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) |
Výsledek
Primární výsledná opatření
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]
Měření sekundárních výsledků
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.]
