(GluEsk) Glutamate and Esketamine (GluEsk)

This interventional trial (n=12) aims to assess the effects of esketamine nasal spray on brain glutamate release, resting state connectivity, and neuroplasticity in patients with depression.

Esketamine, an NMDA receptor antagonist, is hypothesised to increase brain glutamate release, thus potentially restoring synaptic functioning and connectivity in brain regions associated with mood regulation.

The study will involve participants aged 18 to 50 years with a BMI between 18-30 who are fluent in English. Exclusion criteria include significant psychiatric disorders, substance misuse, and contraindications to 7T MRI.

The primary objective is to compare the effect of a single dose of esketamine (56mg intranasal) versus placebo on brain glutamate release measured via 7T fMRS. Secondary objectives include assessing resting state connectivity changes via 7T BOLD-rs-fMRI and neuroplasticity via a computerised visual task.

The study employs a randomised, crossover design with masking and is conducted at the Department of Psychiatry, University of Oxford. Recruitment is estimated to start in June 2024 and complete by June 2025.

Trial Details

Esketamine is the S-enantiomer of racemic ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine and other antidepressant NMDA receptor antagonists are hypothesised to act by producing a rapid increase in brain glutamate release, which then stimulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This activity in turn is thought to restore synaptic functioning, neuroplasticity, and connectivity in brain regions involved in mood regulation, which would be ultimately responsible for the antidepressant effect of esketamine However, the effect of esketamine on glutamate release in humans has not previously been studied. In this study we therefore aim to ascertain the effect of esketamine on brain glutamate release, resting state connectivity, and neuroplasticity as measured via fMRS, BOLD-rs-fMRI, and a behavioural computerised visual task respectively.

NCT Number NCT06432322

Data attribution

A large set of the trials in our database are sourced from ClinicalTrials.gov (CTG). We have modified these post to display the information in a more clear format or to correct spelling mistakes. Our database in actively updated and may show a different status (e.g. completed) if we have knowledge of this update (e.g. a published paper on the study) which isn't reflected yet on CTG. If a trial is not sourced from CTG, this is indicated on this page and you can follow the link to the alternative source of information.