Repurposing Colchicine to Improve Vascular Function in Hypertension

NCT04303689 | Completed DMC

• 1 other identifier: Colchicine study
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Essential Hypertension

Keywords

essential hypertension; colchicine; vascular function; vascular compliance; blood pressure

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Blood pressure

  Measurements are made before and after 3 weeks of treatment with colchicine or placebo.

• Vascular compliance

  Measurements are made before and after 3 weeks of treatment with colchicine or placebo.

Study Arms (2)

Colchicine

EXPERIMENTAL

3 weeks of treatment with colchicine

Drug: Colchicine Tablets

Placebo

PLACEBO COMPARATOR

3 weeks of placebo-treatment

Drug: Placebo

Interventions

Colchicine Tablets DRUG

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

Also known as: Colchicine

Colchicine

Placebo DRUG

patients with essential hypertension are randomized to receive either 3 weeks of placebo-treatment

Placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• smoking
• excessive alcohol use
• chronic diseases (beside essential hypertension)

Sponsors & Collaborators

• University of Copenhagen: lead
• University of Aarhus: collaborator

Study Sites (1)

Department of Nutrition, Exercise and Sports, UCopenhagen

Copenhagen, 2200, Denmark

Location

Related Publications (1)

• Ehlers TS, van der Horst J, Moller S, Piil PK, Gliemann L, Aalkjaer C, Jepps TA, Hellsten Y. Colchicine enhances beta adrenoceptor-mediated vasodilation in men with essential hypertension. Br J Clin Pharmacol. 2023 Jul;89(7):2179-2189. doi: 10.1111/bcp.15688. Epub 2023 Feb 24.

  PMID: 36764326 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Ylva Hellsten, Dr. Med. Sc.

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects are blinded and randomized to receive either colchicine-treatment or placebo
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Dr. Med. Sc.

Model Details: Single blinded randomized placebo-controlled intervention

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: March 11, 2020
• Study Start: August 1, 2020
• Primary Completion: December 1, 2022
• Study Completion: February 28, 2023
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)