Ignite Creation Date:
2024-05-06 @ 11:02 AM
Last Modification Date:
2024-10-26 @ 12:39 PM
Study NCT ID:
NCT03414918
Status:
UNKNOWN
Last Update Posted:
2018-01-30
First Post:
2017-12-27
Brief Title:
Macrolides for KCNJ5 - Mutated Aldosterone-Producing Adenoma MAPA
Sponsor:
University Hospital Padova
Organization:
University Hospital Padova
Study Overview
Official Title:
Macrolides for KCNJ5 - Mutated Aldosterone-Producing Adenoma MAPA A Study Of Personalized Diagnosis of Primary Aldosteronism With Implications For Treatment
Status:
UNKNOWN
Status Verified Date:
2018-01
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MAPA
Brief Summary:
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
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
Detailed Description:
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 Kir34 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None