Ignite Creation Date:
2024-05-06 @ 8:19 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06337994
Status:
COMPLETED
Last Update Posted:
2024-03-29
First Post:
2024-03-23
Brief Title:
Memantine Hydrochloride for Treatment of Cognitive Dysfunction Due to Traumatic Brain Injury
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Treatment of Post-traumatic Cognitive Dysfunction With Memantine Hydrochloride an N-methyl-D-aspartate NMDA-Type Receptor Blocker a Clinical Trial
Status:
COMPLETED
Status Verified Date:
2024-08
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:
Posttraumatic consequences are common causes of disability and long-term morbidity They include cognitive dysfunction seizures headache dizziness fatigue sensory deficits neurodegeneration and psychiatric disorders eg posttraumatic stress disorder depression anxiety etc Diffuse axonal injury and disruption of normal neuronal function are the most common and important pathologic features of traumatic primary closed head injury depression anxiety etc Excitotoxicity and apoptosis caused by activation of N-methyl-D-aspartate NMDA glutamate receptors are two main suggested mechanisms of traumatic neuronal cell death and posttraumtic neurologic adverse consequences Experimental and clinical studies have demonstrated that memantine hydrochloride NMDA-type glutamate receptor antagonist could have beneficial effect in treatment of posttraumatic cognitive dysfunction Memantine may contribute to cognitive improvements in TBI by decreasing the synaptic noise resulting from excessive NMDA receptor activation inhibition of β-amyloid mediated toxicity and readjustment of the balance between inhibition and excitation on neuronal networks in the central nervous system CNS
Detailed Description:
Posttraumatic consequences are common causes of disability and long-term morbidity Traumatic brain injuries TBIs are traditionally classified into primary and secondary injuries Primary brain injury is usually mechanically induced and occurs at the moment of injury while secondary injury is not mechanically induced delayed from the moment of injury and may superimpose a previously injured brain by mechanical forces Primary brain injury may be associated with focal scalp injury skull fractures brain contusion caused by contact ie an object striking the head or the brain striking the inside of the skull as well as diffuse axonal brain injury which is usually caused by acceleration-deceleration forces or rotational acceleration of the brain as a result of unrestricted movement of the head shearing and tensile forces and compressive strains Diffuse axonal injury and disruption of normal neuronal function are the most common and important pathologic features of TBI The latter is mostly microscopic damage and is often not visible in neuroimaging Consequences of TBI include cognitive dysfunction seizures headache dizziness fatigue sensory deficits neurodegeneration and psychiatric disorders eg posttraumatic stress disorder depression anxiety etc Excitotoxicity and apoptosis are two main suggested mechanisms of traumatic neuronal cell death The N-methyl-D-aspartate NMDA glutamate receptors are implicated in these mechanisms Furthermore the activation of NMDA receptors by glutamate promotes the production of reactive oxygen species ROS and nitric oxide NO which further exacerbate secondary cell injury NMDA receptor plays a pivotal role in learning and memory Experimental and clinical studies have demonstrated that memantine hydrochloride NMDA-type glutamate receptor antagonist could have beneficial effect in treatment of posttraumatic cognitive dysfunction Memantine is an FDA-approved drug for the treatment of moderate to severe Alzheimers disease and is also used clinically for the treatment of some patients with Parkinsons disease Memantine is effective in blocking excessive activity of NMDA-type glutamate receptors and reduces the progression of dementia Memantine has shown to be neuroprotective in animal models of cerebral and spinal cord ischemia and in models of TBI Memantine may contribute to cognitive improvements in TBI by decreasing the synaptic noise resulting from excessive NMDA receptor activation inhibition of β-amyloid mediated toxicity and readjustment of the balance between inhibition and excitation on neuronal networks in the CNS It showed beneficial effects in treating post-injury synaptic dysfunction in the neocortex partially reversing deficits in long-term potentiation LTP mitigating pathologic NMDAR loss and reducing tau phosphorylation and β-amyloid expression Memantine spares hippocampal neurons after a single moderatesevere or repetitive TBI and normalizes LTP β-amyloid and tau expressions and neuroinflammation abnormalities in a repeat experimental model of TBI In rodent studies memantine dramatically increased adult hippocampal neurogenesis Memantine does not have the significant negative side effects such as hallucinations and coma of other NMDAR antagonists High doses 20 mgd may cause non-serious side effects eg dizziness anxiety restlessness or agitation
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?:
None
Is an FDA AA801 Violation?:
None