Clinical trial NCT04303689: Repurposing Colchicine to Improve Vascular Function in Hypertension
Official title: Repurposing Colchicine to Improve Vascular Function in Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Essential Hypertension
Keywords: essential hypertension
colchicine
vascular function
vascular compliance
blood pressure
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Aarhus
First posted: 2020-03-11
Enrollment: 31
Sex: MALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single blinded randomized placebo-controlled intervention
Primary purpose: BASIC_SCIENCE

Brief summary: In this project the potential beneficial effect of the drug colchicine on vascular reactivity and blood pressure will be assessed. 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 our own research. 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 the hypothesis 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Changes in vascular function with treatment measured as flowchanges with ultrasound doppler in response to infusions of isoprenaline
timeFrame: Change in vascular conductance in response to infusions is assessed after acute treatment and before and within 72 hours after the 3 weeks of colchicine or placebo treatment
measure: 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 acetylcholine
timeFrame: Change in vascular conductance in response to infusions is assessed after acute treatment before and within 72 hours after the 3 weeks of colchicine or placebo treatment
measure: 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
timeFrame: Change in vascular conductance in response to infusions is assessed after acute treatment and before and within 72 hours after the 3 weeks of colchicine or placebo treatment
Secondary outcomes:
measure: Blood pressure
timeFrame: Measurements are made before and after 3 weeks of treatment with colchicine or placebo.
measure: Vascular compliance
timeFrame: Measurements are made before and after 3 weeks of treatment with colchicine or placebo.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Nutrition, Exercise and Sports, UCopenhagen
Study officials:
affiliation: University of Copenhagen
name: Ylva Hellsten, Dr. Med. Sc.
role: PRINCIPAL_INVESTIGATOR
References: