Ignite Creation Date:
2024-05-06 @ 7:56 PM
Last Modification Date:
2024-10-26 @ 3:17 PM
Study NCT ID:
NCT06190483
Status:
COMPLETED
Last Update Posted:
2024-01-05
First Post:
2023-12-19
Brief Title:
Investigating the Role of Diazepam on Brain Function and Chemistry in Psychosis Risk
Sponsor:
Kings College London
Organization:
Kings College London
Study Overview
Official Title:
Effect of Benzodiazepine on Corticolimbic Activation GABA and Glutamate in Subjects at Clinical High Risk of Psychosis
Status:
COMPLETED
Status Verified Date:
2023-12
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:
BENZOGAP
Brief Summary:
This study will investigate whether a single dose of diazepam 5mg compared to placebo can modulate brain chemistry GABAglutamate levels and function blood flow neural response and connectivity during tasks and at-rest in 24 individuals at clinical high-risk for psychosis
Detailed Description:
The pathophysiology of psychosis involves elevated subcortical dopamine function but the factors driving this are still unclear Evidence from a neurodevelopmental animal model of psychosis suggests that this arises through a pathway linking psychosocial stress corticolimbic hyperresponsivity and GABAglutamate imbalance In response to stressnegative emotion amygdala hyperresponsivity decreases GABA interneuron function in the hippocampus through strong direct projections Decreased hippocampal GABA function leads to disinhibition of hippocampal pyramidal cells elevating local activity and glutamate levels Increased output from the hippocampus to the striatum elevates dopamine release in the striatum and increases the firing of dopaminergic neurons in the midbrain These neurobiological effects are associated with cognitive eg working memory and emotional deficits eg increased anxiety Moreover peripubertal premorbid administration of benzodiazepines at anxiolytic doses to this animal of psychosis is shown to normalise hippocampal activity thereby preventing the emergence of striatal hyperdopaminergia and associated behavioural abnormalities in adulthood Collectively these findings indicate that GABA dysfunction and emotional hyperresponsivity may play a critical role in the development of psychosis in humans and suggest that clinical interventions targeting this pathway have the potential to reduce the risk of developing the disorder
This study will use multimodal neuroimaging MRS ASL rs-fMRI tb-fMRI to assess whether the acute administration of a benzodiazepine can modulate the pathway linking corticolimbic response and GABAglutamate levels in people in the premorbid stage of psychosis at clinical high risk CHR Using a randomised double-blind placebo-controlled crossover design 24 CHR-P participants will undergo two MRI sessions once under an acute oral dose of diazepam 5 mg generic and once under oral placebo 50 mg ascorbic acid with a minimum 3-week washout period between visits
This study will use multimodal neuroimaging MRS ASL rs-fMRI tb-fMRI to assess whether the acute administration of a benzodiazepine can modulate the pathway linking corticolimbic response and GABAglutamate levels in people in the premorbid stage of psychosis at clinical high risk CHR Using a randomised double-blind placebo-controlled crossover design 24 CHR-P participants will undergo two MRI sessions once under an acute oral dose of diazepam 5 mg generic and once under oral placebo 50 mg ascorbic acid with a minimum 3-week washout period between visits
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