Trial record 3 of 24 for:    "Conn's syndrome"

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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01978132
First received: October 31, 2013
Last updated: November 6, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Primary Hyperaldosteronism
Procedure: forearm ischemia and reperfusion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Primary Hyperaldosteronism and Endothelial Ischemia-reperfusion Injury

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • brachial FMD [ Time Frame: 1 day morning ] [ Designated as safety issue: No ]
    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 [ Time Frame: one day morning (just before FMD experiment) ] [ Designated as safety issue: No ]
    Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells


Other Outcome Measures:
  • aldosterone and renin [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.


Enrollment: 40
Study Start Date: November 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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

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

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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01978132

Locations
Netherlands
Radboud University Medical Centre
Nijmegen, Gelderland, Netherlands, 6525EZ
Sponsors and Collaborators
Radboud University
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01978132     History of Changes
Other Study ID Numbers: NL45381.091.13
Study First Received: October 31, 2013
Last Updated: November 6, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Radboud University:
primary hyperaldosteronism
primary hypertension
forearm ischemia-reperfusion
(reduction) in brachial artery FMD
endothelial ischemia-reperfusion injury

Additional relevant MeSH terms:
Hyperaldosteronism
Ischemia
Reperfusion Injury
Wounds and Injuries
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on July 28, 2014