RECTIFHY: Repurposing Colchicine to Improve Vascular Function in Hypertension

Sponsor

University of Copenhagen (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04303689

Collaborator

University of Aarhus (Other)

Enrollment

Location

Arms

32.3

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: Colchicine Tablets Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single blinded randomized placebo-controlled interventionSingle blinded randomized placebo-controlled intervention

Masking:

Single (Participant)

Masking Description:

Subjects are blinded and randomized to receive either colchicine-treatment or placebo

Primary Purpose:

Basic Science

Official Title:

Repurposing Colchicine to Improve Vascular Function in Hypertension

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Apr 10, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colchicine 3 weeks of treatment with colchicine	Drug: Colchicine Tablets patients with essential hypertension are randomized to receive either 3 weeks of colchicine Other Names: 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

Arm

Intervention/Treatment

Experimental: Colchicine

3 weeks of treatment with colchicine

Drug: Colchicine Tablets

patients with essential hypertension are randomized to receive either 3 weeks of colchicine

Other Names:

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

Outcome Measures

Primary Outcome Measures

Changes in vascular function with treatment measured as flowchanges with ultrasound doppler in response to infusions of isoprenaline [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]
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
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 [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]
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
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 after acute treatment and before and within 72 hours after the 3 weeks of colchicine or placebo treatment]
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

Secondary Outcome Measures

Blood pressure [Measurements are made before and after 3 weeks of treatment with colchicine or placebo.]
Blood pressure measured at home with an automated blood pressure device
Vascular compliance [Measurements are made before and after 3 weeks of treatment with colchicine or placebo.]
measured by intraarterial blood pressure and changes in arterial diameter by ultrasound doppler

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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