Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00205712
Status:
COMPLETED
Last Update Posted:
2016-01-14
First Post:
2005-09-13
Brief Title:
Prevention of N-methyl-D-aspartate NMDA Antagonist-induced Psychosis in Kids
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
Prevention of NMDA Antagonist-induced Psychosis and Memory Impairment in Children
Status:
COMPLETED
Status Verified Date:
2016-01
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:
None
Brief Summary:
Ketamine an FDA approved anesthetic agent is becoming the sedativeanalgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents However emergence reactions are an important adverse effect of ketamine characterized by transient changes in cognitive function dissociation and mild schizophrenia-like symptoms These cognitive and behavioral effects are dose-dependently induced by ketamine and other antagonists of the N-methyl-D-aspartate NMDA glutamate receptor NMDA receptor hypofunction can disinhibit excitatory cholinergicglutamatergic projections in key areas of the brain and this has been proposed to explain key features of schizophrenia Several treatments that block excessive excitatory transmitter release have also been shown to prevent cognitive and behavioral effects of ketamine-induced NMDA receptor hypofunction in humans Alpha-2 adrenergic agonists which can presynaptically inhibit acetylcholine release can prevent mild ketamine-induced behavioral and cognitive symptoms in healthy human adults However this prevention strategy has not been evaluated in children Children currently receive clinically-indicated treatment with the NMDA antagonist ketamine and this age group is an important target for pharmacological strategies aimed at the prevention of schizophrenia This application proposes a double-blind placebo-controlled randomized trial to test the safety and effectiveness of dexmedetomidine an FDA approved alpha-2 adrenergic agonist in preventing ketamine-induced mental symptoms in children Planned primary analyses will evaluate effects of the hypothesized prevention treatment on clinical and cognitive variables using analysis of variance ANOVA The proposed experiments are relevant to future prevention trials for individuals at risk for schizophrenia and to preventing adverse effects of NMDA antagonist anesthetic agents ketamine nitrous oxide
Detailed Description:
The proposed study will be conducted using existing dedicated clinical and research space in St Louis Childrens Hospitals Emergency Department Pediatric Clinical Research Center PCRC and Orthopedic Clinic This project has 3 major aims and 1 exploratory aim addressed by a prospective randomized blinded placebo controlled drug trial to test whether a pharmacological strategy can prevent NMDA receptor hypofunction-induced behavioral and cognitive dysfunction in pre- and post-pubertal children Based on previous preclinical and clinical research on the effects and blockade of the effects of ketamine and similar compounds the study investigators have carefully selected a dose of the alpha-2 adrenergic agonist dexmedetomidine that will permit this study to be conducted with low risk to enrolled subjects who are undergoing clinically-indicated ketamine sedation for forearm fracture reduction
General Experimental Design This project will test the safety and effectiveness of dexmedetomidine for preventing ketamine-induced behavioral and cognitive symptoms in healthy human children undergoing clinically indicated ketamine sedation for forearm fracture reduction
Aims 1 and 2 will be addressed by randomized blinded administration of dexmedetomidine or saline placebo to ketamine-sedated subjects to test the efficacy of dexmedetomidine in preventing ketamine-induced behavioral and cognitive changes during recovery from sedation
Aim 3 will be addressed by comparing between the subjects randomized to receive dexmedetomidine or saline placebo measurements of distress and frequency of adverse cardiopulmonary effects during sedation fracture-reduction and recovery
General Experimental Design This project will test the safety and effectiveness of dexmedetomidine for preventing ketamine-induced behavioral and cognitive symptoms in healthy human children undergoing clinically indicated ketamine sedation for forearm fracture reduction
Aims 1 and 2 will be addressed by randomized blinded administration of dexmedetomidine or saline placebo to ketamine-sedated subjects to test the efficacy of dexmedetomidine in preventing ketamine-induced behavioral and cognitive changes during recovery from sedation
Aim 3 will be addressed by comparing between the subjects randomized to receive dexmedetomidine or saline placebo measurements of distress and frequency of adverse cardiopulmonary effects during sedation fracture-reduction and recovery
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-0886 | OTHER | Washington University IRB | None |