Primary AldosteronismNCT05686993
Effect of a Proposed Cav1.3 Inhibitor in Primary Aldosteronism
A study testing Cinnarizine and NIFEdipine ER in people with Primary Aldosteronism and Endocrine Hypertension, run by Queen Mary University of London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Primary Aldosteronism, Endocrine Hypertension
- What is being tested?
- Cinnarizine and NIFEdipine ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 24 Apr 2023to 6 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed PA, as demonstrated by a positive screening test and internationally endorsed confirmatory test (saline suppression test, captopril challenge test)
- Adults > 18 years of age
- Able and willing to give informed consent
Who cannot join
- Uncontrolled hypertension requiring use of MRA
- Unwilling or unable to give consent
- Below age 18 or above age 90 years
- Allergy to cinnarizine or nifedipine or their excipients
- Existing use of cinnarizine or nifedipine for an alternative indication
- Breastfeeding or pregnant women
Show all 12Show fewer
- Diagnosis of Parkinson's disease
- Severe hepatic or renal insufficiency
- Concurrent use of sedating central nervous system (CNS) depressants or rifampicin
- Porphyria
- Cardiogenic shock, clinically significant aortic stenosis, unstable angina, within one month of a myocardial infarction
- Previous gastro-intestinal or oesophageal obstruction or ileostomy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of a Proposed Cav1.3 Inhibitor in Primary Aldosteronism - a Pilot Study
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.
Read the 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.
- Conditions
- Primary Aldosteronism, Endocrine Hypertension
- Being tested
- Cinnarizine, NIFEdipine ER
- Keywords
- Primary aldosteronism, Calcium channel blocker, Aldosterone
- Medical subject headings
- Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CinnarizineDrug
Also called Stugeron, Stunarone, Cinarin
Cinnarizine oral 30mg TDS
NIFEdipine ERDrug
Also called Adalat, Adipine, Coracten, Fortipine, Nifedipress
Nifedipine oral 60mg daily extended release
| Study group | Role | What they receive |
|---|---|---|
| Cinnarizine and nifedipine | Experimental | Drug 1 for 2 weeks, 2 weeks of washout, then Drug 2 for 2 weeks Drug 1 and 2, in no specified order, Cinnarizine 30 mg oral TDS and Nifedipine 60 mg oral daily Receives: Drug: Cinnarizine; Drug: NIFEdipine ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aldosterone change
Evaluate whether the effect of calcium channel blockade on plasma aldosterone levels is due primarily to Cav1.3 blockade in individuals with PA and clinical features suggesting an increased likelihood of a CACNA1D mutation.
Measured: 6 weeks
Secondary outcomes (1)
Blood pressure change
Evaluate whether the use of a proposed Cav1.3 inhibitor affects blood pressure in individuals with PA, evaluating both systolic blood pressure and diastolic blood pressure.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2023
- Study start24 Apr 2023
- Primary completion1 Sep 2023
- Study completion6 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary AldosteronismStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Treatment with 2 study drugs with 2 weeks of drug washout in between Study drug treatments are: cinnarizine for 2 weeks, nifedipine for 2 weeks Order randomly determined by computer program, with results released by an independent clinician as patients are recruited
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Morris Brown, MD FRCP, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05686993
- Sponsor's protocol ID
- 154739
- Status last verified
- Jul 2024
- First submitted
- 22 Dec 2022
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ng E, Lee YN, Taylor A, Shaheen F, Azizan E, Drake WM, Brown MJ. Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor. J Clin Endocrinol Metab. 2025 Sep 16;110(10):2752-2761. doi: 10.1210/clinem/dgaf081.
PubMed 40052842
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Proposed Cav1.3 Inhibitor in Primary Aldosteronism - a Pilot Study
- ClinicalTrials.gov ID
- NCT05686993
- Acronym / sponsor ID
- 154739
- Conditions
- Primary Aldosteronism, Endocrine Hypertension
- Keywords
- Primary aldosteronism, Calcium channel blocker, Aldosterone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 6 Sep 2023 (actual)
- First posted
- 17 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Treatment with 2 study drugs with 2 weeks of drug washout in between Study drug treatments are: cinnarizine for 2 weeks, nifedipine for 2 weeks Order randomly determined by computer program, with results released by an independent clinician as patients are recruited
| Arm | Type | Receives |
|---|---|---|
| Cinnarizine and nifedipine | Experimental | Drug: Cinnarizine, Drug: NIFEdipine ERDrug 1 for 2 weeks, 2 weeks of washout, then Drug 2 for 2 weeks Drug 1 and 2, in no specified order, Cinnarizine 30 mg oral TDS and Nifedipine 60 mg oral daily |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed PA, as demonstrated by a positive screening test and internationally endorsed confirmatory test (saline suppression test, captopril challenge test)
- Adults > 18 years of age
- Able and willing to give informed consent
Key exclusion criteria (12 listed)
- Uncontrolled hypertension requiring use of MRA
- Unwilling or unable to give consent
- Below age 18 or above age 90 years
- Allergy to cinnarizine or nifedipine or their excipients
- Existing use of cinnarizine or nifedipine for an alternative indication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CinnarizineAlso: Stugeron, Stunarone, CinarinCinnarizine oral 30mg TDS | Drug | Cinnarizine and nifedipine |
| NIFEdipine ERAlso: Adalat, Adipine, Coracten, Fortipine, NifedipressNifedipine oral 60mg daily extended release | Drug | Cinnarizine and nifedipine |
Primary outcome
Aldosterone change
Time frame: 6 weeks
Evaluate whether the effect of calcium channel blockade on plasma aldosterone levels is due primarily to Cav1.3 blockade in individuals with PA and clinical features suggesting an increased likelihood of a CACNA1D mutation.
1 secondary outcome
Blood pressure change
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
- Derived from this study: PubMed 40052842Ng E, Lee YN, Taylor A, Shaheen F, Azizan E, Drake WM, Brown MJ. Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor. J Clin Endocrinol Metab. 2025 Sep 16;110(10):2752-2761. doi: 10.1210/clinem/dgaf081.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morris Brown, MD FRCP principal investigator
Queen Mary University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cinnarizine and NIFEdipine ER in people with Primary Aldosteronism and Endocrine Hypertension, run by Queen Mary University of London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aldosterone change (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05686993, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024; AzTrials last refreshed its copy on 8 Nov 2026.