Repurposing Colchicine to Improve Vascular Function in Hypertension (RECTIFHY)

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.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Colchicine Tablets; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • Department of Nutrition, Exercise and Sports, UCopenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: University of Aarhus
• Investigators: Principal Investigator: Ylva Hellsten, Dr. Med. Sc., University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: blood pressure; vascular function; colchicine; essential hypertension; vascular compliance
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: Colchicine study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No