Primary Hyperaldosteronism and Ischemia-reperfusion Injury

NCT ID: NCT01978132

Last Updated: 2017-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2017-07-01

Brief Summary

Patients with primary hyperaldosteronism experience more cardiovascular events compared to patients with primary hypertension, independent of the blood pressure level.

In this research we hypothesize that patients with primary hyperaldosteronism are more susceptible to ischemia-reperfusion injury.

Detailed Description

Patients with PHA have an increased risk of cardiovascular events, independent of blood pressure level. Also in patients suffering a myocardial infarction, circulating aldosterone levels are associated with increased mortality. In animal models of myocardial infarction, the administration of exogenous aldosterone increased infarct size, although other studies did not report this effect. In similar models, antagonists of the mineralocorticoid receptor (MR) reduced infarct size, which was completely abolished in ecto-5'-nucleotidase (CD73, the enzyme that catalyses extracellular formation of the endogenous nucleoside adenosine) and adenosine receptor knock-out mice. Therefore, we hypothesize that patients with PHA have an increased susceptibility for ischemia-reperfusion (IR)-injury due to down-regulation of the enzyme CD73. We will use the reduction in brachial flow-mediated dilation (FMD) by forearm IR as a well-validated endpoint for (endothelial) IR-injury.

Conditions

Primary Hyperaldosteronism

Keywords

primary hyperaldosteronism; primary hypertension; forearm ischemia-reperfusion; (reduction) in brachial artery FMD; endothelial ischemia-reperfusion injury

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Primary hyperaldosteronism

patients with primary hyperaldosteronism will be subjected to the intervention forearm ischemia and reperfusion (20 minutes of forearm ischemia and 20 minutes of reperfusion).

Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury

Group Type: ACTIVE_COMPARATOR

forearm ischemia and reperfusion

Intervention Type: PROCEDURE

both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.

Primary hypertension

Patients with primary hypertension (PHA excluded)will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.

Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury

Group Type: PLACEBO_COMPARATOR

forearm ischemia and reperfusion

Intervention Type: PROCEDURE

both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.

Interventions

forearm ischemia and reperfusion

both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age 18-75 years
• Confirmed primary hyperaldosteronism (aldosterone >0.28 nmol/l after salt loading)
• Serum potassium ≥ 3.5 mmol/L (with or without potassium supplementation)
• Written informed consent

• Age 18-75 years
• Primary hypertension
• Baseline aldosterone <0.30 nmol/l and aldosterone-renin-ratio<0.09
• Serum potassium ≥ 3.5 mmol/L
• Written informed consent

Exclusion Criteria

• Smoking
• History of atherosclerotic disease (myocardial infarction (MI), stroke, or peripheral vascular disease)
• Not possible to change the antihypertensive medication into only diltiazem with or without hydralazine, according to the treating physician.
• Not possible to temporarily interrupt statin treatment, if the patient use statins, according to the treating physician.
• Severe renal dysfunction (MDRD < 30 ml/min)
• Second/third degree AV-block on electrocardiography
• Cardiac failure
• Diabetes Mellitus
• Use of acetylsalicylic acid and NSAID's theophylline, and dipyridamole

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

NL45381.091.13

Identifier Type: -

Identifier Source: org_study_id