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Primary Hyperaldosteronism and Ischemia-reperfusion Injury (PHA-FMD)

Primary Purpose

Primary Hyperaldosteronism

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
forearm ischemia and reperfusion
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Primary Hyperaldosteronism focused on measuring primary hyperaldosteronism, primary hypertension, forearm ischemia-reperfusion, (reduction) in brachial artery FMD, endothelial ischemia-reperfusion injury

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Radboud University Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Primary hyperaldosteronism

Primary hypertension

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

CD73 and adenosine
Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells

Full Information

First Posted
October 31, 2013
Last Updated
October 11, 2017
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01978132
Brief Title
Primary Hyperaldosteronism and Ischemia-reperfusion Injury
Acronym
PHA-FMD
Official Title
Primary Hyperaldosteronism and Endothelial Ischemia-reperfusion Injury
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
May 1, 2017 (Actual)
Study Completion Date
July 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperaldosteronism
Keywords
primary hyperaldosteronism, primary hypertension, forearm ischemia-reperfusion, (reduction) in brachial artery FMD, endothelial ischemia-reperfusion injury

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Primary hyperaldosteronism
Arm Type
Active Comparator
Arm Description
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
Arm Title
Primary hypertension
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
forearm ischemia and reperfusion
Intervention Description
both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion.
Primary Outcome Measure Information:
Title
brachial FMD
Description
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)
Time Frame
1 day morning
Secondary Outcome Measure Information:
Title
CD73 and adenosine
Description
Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells
Time Frame
one day morning (just before FMD experiment)
Other Pre-specified Outcome Measures:
Title
aldosterone and renin
Description
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.
Time Frame
1 day
Title
leukocyte telomere length (LTL)
Description
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
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Radboud University Medical Centre
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525EZ
Country
Netherlands

12. IPD Sharing Statement

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Primary Hyperaldosteronism and Ischemia-reperfusion Injury

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