Hyperaldosteronism Clinical Trial
Official title:
Macrolides for KCNJ5 - Mutated Aldosterone-Producing Adenoma (MAPA): A Study Of Personalized Diagnosis of Primary Aldosteronism With Implications For Treatment
This study evaluates if :
1 ) the plasma aldosterone concentration and blood pressure change in response to
roxithromycin could be useful for the screening of PA patients carrying a KCNJ5-mutated APA;
2) the change of PAC in response to mutated KCNJ5 channel is truly occurring in KCNJ5-mutated
APA.
Aldosterone-producing adenoma (APA) cause primary aldosteronism (PA), the main curable cause
of endocrine hypertension, is in up to 66% of all cases investigated with adrenal vein
sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of APA and cause
the most florid PA phenotypes. The recent finding that macrolide antibiotics specifically
inhibit in vitro the altered function of mutated KCNJ5 channels has opened new horizons for
the diagnosis and treatment of APA with KCNJ5 mutations in that it can allow identification
and target treatment of PA patients harbouring a mutated APA. Thus, the aim of the present
study was to investigate if clarithromycin and roxithromycin, two macrolides that potently
blunt mutated Kir3.4 channel function in vitro, affect plasma aldosterone concentration in
adrenal vein blood during AVS and in peripheral blood, respectively, in PA patients with a
mutated APA.
The investigators designed two proof of concept studies. In study A: consecutive patients
with an unambiguous biochemical evidence of PA will be exposed to a single dose of 250 mg
clarithromycin during AVS, to assess its effect on the relative aldosterone secretion index
(RASI) in adrenal vein blood from the gland with and without APA. In study B: consecutive
hypertensive patients submitted to the work-up for hypertension will receive a single oral
dose of 150 mg roxithromycin. The experimental endpoints will be the change induced by
roxithromycin of plasma aldosterone concentration (PAC) and other steroids, direct active
renin concentration (DRC), serum K+, systolic and diastolic blood pressure.
The investigators expect to prove that: i) clarithromycin allows identification of mutated
APA before adrenalectomy and sequencing of tumour DNA; ii) the acute changes of PAC, DRC, and
blood pressure in peripheral venous blood after roxithromycin can be a proxy for the presence
of an APA with somatic mutations.
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