Primary Hyperaldosteronism and Ischemia-reperfusion Injury

Primary Hyperaldosteronism Clinical Trial

— PHA-FMD  

Official title:

Primary Hyperaldosteronism and Endothelial Ischemia-reperfusion Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01978132
• Other study ID #: NL45381.091.13
• Status: Completed
• Phase: N/A
• First received: October 31, 2013
• Last updated: October 11, 2017
• Start date: November 2013
• Est. completion date: July 1, 2017

Study information

• Verified date: April 2017
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 1, 2017
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria patients with primary hyperaldosteronism:

• 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

Inclusion Criteria patients with primary hypertension:

• 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 for both arms (patients with primary hyperaldosteronism and patients with primary hypertension:

• 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

Related Conditions & MeSH terms

• Hyperaldosteronism
• Ischemia
• Primary Hyperaldosteronism
• Reperfusion Injury

Intervention

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

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	aldosterone and renin	Just before the FMD experiment, blood will be drawn for aldosterone and renin levels. These levels will not be determined, unless the brachial artery FMD after ischemia and reperfusion is significantly reduced in patients with primary hyperaldosteronism. We will store the plasma and serum at -20 C. If applicable, the aldosterone and aldosterone-to-renin ratio will be determined to correlate the primary outcome measure to the aldosterone and ARR levels.	1 day
Other	leukocyte telomere length (LTL)	We will measure LTL in 12 patients with PHA and 12 patients with EHT to assess wether aldosterone excess increases telomere shortening in patients with PHA	1 day
Primary	brachial FMD	primary outcome measure is the reduction in brachial artery FMD after 20 minutes of forearm ischemia and 20 minutes of reperfusion in patients with primary hyperaldosteronism (compared to patients with primary hypertension)	1 day morning
Secondary	CD73 and adenosine	Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells	one day morning (just before FMD experiment)