Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06432322
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-27
First Post:
2024-05-21
Brief Title:
GluEsk Glutamate and Esketamine
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
Effects of Esketamine Challenge on Brain Glutamate Release fMRS Resting State Connectivity BOLD-rs-fMRI and Neuroplasticity Visual Task
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
GluEsk
Brief Summary:
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 dynamic brain glutamate release resting state connectivity and neuroplasticity as measured via fMRS BOLD-rs-fMRI and a behavioural computerised visual task respectively
Detailed Description:
There is growing interest in the use of antagonists at the glutamate N-methyl-D-aspartate NMDA receptor in patients with treatment-resistant depression TRD Work in animal studies suggests that NMDA receptor antagonists act initially by increasing brain glutamate release but whether such an action occurs in humans is not established
Esketamine is the S-enantiomer of racemic ketamine a non-selective non-competitive antagonist of the ionotropic glutamate NMDA receptor It is the only NMDA receptor antagonist licensed in the UK for the treatment of patients with TRD Esketamine is administered intranasally it is rapidly absorbed by the nasal mucosa following nasal administration and can be measured in plasma within 7 minutes following a 28 mg dose The time to reach maximum plasma concentration tmax is typically 20 to 40 minutes after the last nasal spray of a treatment session It is hypothesised that through NMDA receptor antagonism esketamine produces a transient increase in glutamate release leading to increases in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPA receptor stimulation and subsequently to increases in neurotrophic signalling which may contribute to the restoration of synaptic function neuroplasticity and connectivity in brain regions involved with the regulation of mood
Glutamate is the primary excitatory neurotransmitter in the brain and has been implicated in several neuropsychiatric disorders Gold-standard methods to assess glutamate activity in the living human brain are expensive and involve radioactive injections and invasive blood sampling More recently preliminary work in our Clinical Psychopharmacology laboratory Department of Psychiatry University of Oxford has shown that 7T fMRS a more widely available non-invasive safe technique that uses a visual stimulus flickering checkerboard can reliably and sensitively measure changes in brain glutamate release No prior study however has shown whether this effect is susceptible to pharmacological challenge We therefore propose to assess whether through its NMDAAMPA-mediated activity esketamine induced glutamate increase can be measured via this fMRS technique
The aims of this study are to investigate the effect of esketamine on brain glutamate release and resting state connectivity and on vision Therefore the primary objective of this study is to assess the effect of a single dose of esketamine 56mg intranasal vs placebo on brain glutamate release changes measured via 7T fMRS flickering checkerboard stimulus Secondary objectives include the investigation of the effects of esketamine on brain resting state connectivity changes measured via 7T BOLD-rs-fMRI and on vision measured via a behavioural computerised visual task Psychological questionnaires will also be measured to check for possible correlations with the outcomes measured
Esketamine is the S-enantiomer of racemic ketamine a non-selective non-competitive antagonist of the ionotropic glutamate NMDA receptor It is the only NMDA receptor antagonist licensed in the UK for the treatment of patients with TRD Esketamine is administered intranasally it is rapidly absorbed by the nasal mucosa following nasal administration and can be measured in plasma within 7 minutes following a 28 mg dose The time to reach maximum plasma concentration tmax is typically 20 to 40 minutes after the last nasal spray of a treatment session It is hypothesised that through NMDA receptor antagonism esketamine produces a transient increase in glutamate release leading to increases in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPA receptor stimulation and subsequently to increases in neurotrophic signalling which may contribute to the restoration of synaptic function neuroplasticity and connectivity in brain regions involved with the regulation of mood
Glutamate is the primary excitatory neurotransmitter in the brain and has been implicated in several neuropsychiatric disorders Gold-standard methods to assess glutamate activity in the living human brain are expensive and involve radioactive injections and invasive blood sampling More recently preliminary work in our Clinical Psychopharmacology laboratory Department of Psychiatry University of Oxford has shown that 7T fMRS a more widely available non-invasive safe technique that uses a visual stimulus flickering checkerboard can reliably and sensitively measure changes in brain glutamate release No prior study however has shown whether this effect is susceptible to pharmacological challenge We therefore propose to assess whether through its NMDAAMPA-mediated activity esketamine induced glutamate increase can be measured via this fMRS technique
The aims of this study are to investigate the effect of esketamine on brain glutamate release and resting state connectivity and on vision Therefore the primary objective of this study is to assess the effect of a single dose of esketamine 56mg intranasal vs placebo on brain glutamate release changes measured via 7T fMRS flickering checkerboard stimulus Secondary objectives include the investigation of the effects of esketamine on brain resting state connectivity changes measured via 7T BOLD-rs-fMRI and on vision measured via a behavioural computerised visual task Psychological questionnaires will also be measured to check for possible correlations with the outcomes measured
Study Oversight
Has Oversight DMC:
None
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?:
False
Is an FDA AA801 Violation?:
None