Ignite Creation Date:
2024-05-05 @ 5:16 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00423943
Status:
COMPLETED
Last Update Posted:
2017-09-29
First Post:
2007-01-16
Brief Title:
Modafinil for Treatment of Cognitive Dysfunction in Schizophrenia
Sponsor:
University of California Los Angeles
Organization:
University of California Los Angeles
Study Overview
Official Title:
Modafinil for Treatment of Cognitive Dysfunction in Schizophrenia
Status:
COMPLETED
Status Verified Date:
2017-08
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:
Patients with schizophrenia have problems in thinking known as cognitive dysfunction This appears to be responsible for their difficulties in social and occupational functioning One particular cognitive function that may be important for schizophrenia is called context processing This refers to the ability to properly use information in the environment to guide thinking and behavior so that it is appropriate to the present circumstance Problems with this function may explain why patients with schizophrenia think and act in unusual ways and often have problems managing aspects of their lives that healthy adults take for granted This cognitive function depends on a region of the brain called the prefrontal cortex which shows impaired function in schizophrenia as well Unfortunately the biochemical aspects of this dysfunction are presently unknown and it is not clear whether current psychiatric medications can improve this function A recent FDA-approved medication that may improve this function is modafinil Studies in animals and healthy adults show that this medication can improve cognitive functions which are related to context processing We plan to study the effects of modafinil on context processing and the brain activity that underlies this function We will use functional MRI and electrophysiology to examine the effects of modafinil both after a single dose and after sustained 4 week treatment We predict that when patients receive modafinil they will perform better on cognitive tests and have improved activity in the regions of the brain that are responsible for these cognitive processes
Detailed Description:
Schizophrenia is a disorder of cognition The cognitive deficits of schizophrenia are present at the onset of the disorder prior to medication exposure are persistent during periods of remission and are strongly related to functional outcome These deficits prominently include prefrontal-dependent functions While existing medications effectively treat psychotic symptoms they exhibit modest benefit at best for cognitive dysfunction Studies of cognition in animal models indicate that the neurotransmitter systems that mediate prefrontal-dependent cognitive processes are not generally augmented by existing antipsychotic medications Therefore advances in the treatment of schizophrenia will require the study of agents with novel pharmacological profiles to establish their potential to remediate cognitive dysfunction
Advances in understanding the mechanism of action of these agents will also require the integration of pharmacology with a sophisticated methodology for testing cognition This goal has been strongly pursued in recent years with the use of functional magnetic resonance imaging fMRI to study pharmacological effects on cognition fMRI studies have identified the cortical network subserving cognitive control and working memory which are consistently impaired among schizophrenia patients The study of medication effects on these processes with fMRI pharmaco-fMRI will permit the more precise delineation of the cognitive mechanisms amenable to pharmacological intervention
This study will use fMRI to study the effects of modafinil on the functional neuroanatomy underlying prefrontal cognitive processes Modafinil is an FDA-approved medication with a unique pharmacological profile and an increasing range of off-label indications Its neurochemical effects in animal models include elevation of extracellular dopamine DA noradrenaline NA and glutamate in the neocortex This profile is favorable for the enhancement of prefrontal cognitive processes These neurochemical effects also appear to be selective for cortical versus subcortical brain regions suggesting that modafinil may have minimal effects on psychotic symptoms or extrapyramidal autonomic and hormonal side effects In addition it differs from amphetamine in structure neurochemical profile and behavioral effects with a lower risk of addictive or cerebrovascular effects Recent studies in animal models healthy adults and adults with psychiatric and neurological disorders indicate that modafinil improves prefrontal cognitive functions This suggests that modafinil is a leading candidate for the treatment of cognitive dysfunction in schizophrenia We aim to test modafinil effects on these processes in healthy adults in order to evaluate modafinil effects on normal-range cognition and then evaluate the remediation of deficits in these functions in individuals with schizophrenia both in a single-dose trial and followed by a trial of sustained treatment
Comparison 1 The effect in healthy adults and adults with schizophreniaschizoaffective disorder of Modafinil 200 milligrams single oral dose versus placebo double-blind balanced crossover design on cognitive control task performance and on activity of dorsolateral prefrontal cortical DLPFC during context processing and anterior cingulate cortex ACC during conflict monitoring phases of the task both measured by fMRI
Comparison 2 The effect in adults with schizophreniaschizoaffective disorder of 4-week randomized double-blind treatment with Modafinil 200 milligrams daily versus placebo on cognitive control task performance and on activity of dorsolateral prefrontal cortical DLPFC during context processing and anterior cingulate cortex ACC during conflict monitoring phases of the task both measured by fMRI
Advances in understanding the mechanism of action of these agents will also require the integration of pharmacology with a sophisticated methodology for testing cognition This goal has been strongly pursued in recent years with the use of functional magnetic resonance imaging fMRI to study pharmacological effects on cognition fMRI studies have identified the cortical network subserving cognitive control and working memory which are consistently impaired among schizophrenia patients The study of medication effects on these processes with fMRI pharmaco-fMRI will permit the more precise delineation of the cognitive mechanisms amenable to pharmacological intervention
This study will use fMRI to study the effects of modafinil on the functional neuroanatomy underlying prefrontal cognitive processes Modafinil is an FDA-approved medication with a unique pharmacological profile and an increasing range of off-label indications Its neurochemical effects in animal models include elevation of extracellular dopamine DA noradrenaline NA and glutamate in the neocortex This profile is favorable for the enhancement of prefrontal cognitive processes These neurochemical effects also appear to be selective for cortical versus subcortical brain regions suggesting that modafinil may have minimal effects on psychotic symptoms or extrapyramidal autonomic and hormonal side effects In addition it differs from amphetamine in structure neurochemical profile and behavioral effects with a lower risk of addictive or cerebrovascular effects Recent studies in animal models healthy adults and adults with psychiatric and neurological disorders indicate that modafinil improves prefrontal cognitive functions This suggests that modafinil is a leading candidate for the treatment of cognitive dysfunction in schizophrenia We aim to test modafinil effects on these processes in healthy adults in order to evaluate modafinil effects on normal-range cognition and then evaluate the remediation of deficits in these functions in individuals with schizophrenia both in a single-dose trial and followed by a trial of sustained treatment
Comparison 1 The effect in healthy adults and adults with schizophreniaschizoaffective disorder of Modafinil 200 milligrams single oral dose versus placebo double-blind balanced crossover design on cognitive control task performance and on activity of dorsolateral prefrontal cortical DLPFC during context processing and anterior cingulate cortex ACC during conflict monitoring phases of the task both measured by fMRI
Comparison 2 The effect in adults with schizophreniaschizoaffective disorder of 4-week randomized double-blind treatment with Modafinil 200 milligrams daily versus placebo on cognitive control task performance and on activity of dorsolateral prefrontal cortical DLPFC during context processing and anterior cingulate cortex ACC during conflict monitoring phases of the task both measured by fMRI
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