Repurposing Colchicine to Improve Vascular Function in Hypertension

Essential Hypertension Clinical Trial

— RECTIFHY  

Official title:

Repurposing Colchicine to Improve Vascular Function in Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04303689
• Other study ID #: Colchicine study
• Status: Completed
• Phase: N/A
• Start date: August 1, 2020
• Est. completion date: February 28, 2023

Study information

• Verified date: May 2023
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: February 28, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Colchicine Tablets
patients with essential hypertension are randomized to receive either 3 weeks of colchicine
• Placebo
patients with essential hypertension are randomized to receive either 3 weeks of placebo-treatment

Locations

Country	Name	City	State
Denmark	Department of Nutrition, Exercise and Sports, UCopenhagen	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University of Copenhagen	University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in vascular function with treatment measured as flowchanges with ultrasound doppler in response to infusions of isoprenaline	Infusions of isoprenalin in the brachial artery, measurement of blood flow with ultrasound doppler and intraarterial blood pressure with an intraarterial transducer for the calculation of leg vascular conductance	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
Primary	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	Infusions of acetylcholine in the brachial artery, measurement of blood flow with ultrasound doppler and intraarterial blood pressure with an intraarterial transducer for the calculation of leg vascular conductance	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
Primary	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	Infusions of sodium nitroprusside in the brachial artery, measurement of blood flow with ultrasound doppler and intraarterial blood pressure with an intraarterial transducer for the calculation of leg vascular conductance	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	Blood pressure	Blood pressure measured at home with an automated blood pressure device	Measurements are made before and after 3 weeks of treatment with colchicine or placebo.
Secondary	Vascular compliance	measured by intraarterial blood pressure and changes in arterial diameter by ultrasound doppler	Measurements are made before and after 3 weeks of treatment with colchicine or placebo.