Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT05686993 |
Other study ID # |
154739 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
May 5, 2023 |
Est. completion date |
May 6, 2024 |
Study information
Verified date |
February 2024 |
Source |
Queen Mary University of London |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The goal of this pilot, open-label prospective study is to evaluate if the effect of calcium
channel blockade on plasma aldosterone levels in people with primary aldosteronism (PA) is
due primarily to Cav1.3 blockade.
This will be tested by treating participants who have PA with both cinnarizine (Cav1.3
blocker) and nifedipine (Cav1.2 blocker) and evaluating effect on aldosterone levels and
blood pressure over a two week course of treatment.
Description:
Medical treatment for Primary Aldosteronism (PA) is currently limited to mineralocorticoid
receptor antagonists (MRA), the most widely available of which is spironolactone. This can
cause numerous adverse effects, especially in men, due to interference with androgen and
progesterone signalling. Hence, alternative drug targets are needed, one potential of which
is Cav1.3.
The CACNA1D mutation in PA affects the calcium channel Cav1.3. Cav1.3 inhibition may offer
targeted treatment for patients with mutations in CACNA1D. Cav1.3 has been a candidate for
novel inhibitors of aldosterone production,4 for which the case is enhanced if
CACNA1D-mutations underlie the above-described phenotype of PA (asymmetric disease leading to
failure to achieve cure with adrenalectomy).
The calcium-channel blocker, cinnarizine, typically used for vertigo and nausea, has been
identified to fit the recently described crystal structure of Cav1.3. This raises the
possibility of using this drug to assess the effect of Cav1.3 inhibition in PA. This may lead
to further studies involving randomisation and placebo to determine if Cav1.3 inhibition is
an important method by which aldosterone levels can be lowered in people with PA.
This study seeks to explore whether the effect of calcium channel blockade on aldosterone
levels in people with PA is due to Cav1.3 blockade, by comparing cinnarizine (proposed Cav1.3
inhibitor) to a conventional calcium channel blocker nifedipine (Cav1.2 inhibitor).
Cinnarizine is not a likely prospect for long-term treatment of PA, because of its potential
additional actions as well as Cav1.3 blockade, but using it in this setting, for a short
period of time, allows exploration of a property of this existing drug (Cav1.3 inhibition).
Outcomes could form the basis of further exploration of this mechanism for future PA
treatments.