Ignite Creation Date:
2025-12-25 @ 1:22 AM
Ignite Modification Date:
2026-01-06 @ 9:10 AM
Study NCT ID:
NCT05686993
Status:
COMPLETED
Last Update Posted:
2024-07-08
First Post:
2022-12-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of a Proposed Cav1.3 Inhibitor in Primary Aldosteronism
Sponsor:
Queen Mary University of London
Organization:
Study Overview
Official Title:
Effect of a Proposed Cav1.3 Inhibitor in Primary Aldosteronism - a Pilot Study
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
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:
None
Brief 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.
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.
Detailed 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.
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.
Study Oversight
Has Oversight DMC:
False
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?:
None
Is an FDA AA801 Violation?: