The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS): study protocol for a randomised controlled, experimental medicine study

Abstract

BackgroundThe discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour.MethodsThe Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737.DiscussionThe results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected.Trial registrationISRCTN, ISRCTN33631053. Retrospectively registered on 8 June 2018 (applied 17 May 2018).Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3175-0) contains supplementary material, which is available to authorized users.

The association of antihypertensive use and depressive symptoms in a large older population with hypertension living in Australia and the United States: a cross-sectional study

“…On the other hand, their use as monotherapy for hypertension was associated with increased hospitalisation for mood disorders [32]. An ongoing trial of CCB focusing on mood symptoms and cognition might provide more evidence for this in the near future [37].…”

Onset and recurrence of psychiatric disorders associated with anti-hypertensive drug classes

“…However, as a caveat, over 90% of patients in the CCB cohorts were taking amlodipine, verapamil, or diltiazem, which all have low brain penetrability and/or limited channel subtype selectivity 37 . Hence the possibility that more brain penetrant, brain selective, CCBs might be of value for psychiatric indications remains to be tested 38,39 . This could be done in conjunction with the evaluation of ARBs, which have also been proposed to be of use for psychiatric indications 40 .…”

Targeting microglia L‐type voltage‐dependent calcium channels for the treatment of central nervous system disorders

“…Similarly, it is not clear whether L-VDCC antagonist drugs are effective in the treatment of bipolar disorder due to inadequate clinical trials, despite extensive clinical use and a clear genetic link between CACNA1C polymorphisms in bipolar disorder (Cipriani et al, 2016). A randomized, double-blind, placebo-controlled trial examining the L-VDCC antagonist nicardipine for mood stabilization was recently initiated (Atkinson et al, 2019).…”