Modafinil Effects on Cognition in Schizophrenia Patients

Phase 4

Completed

• Conditions: Schizophrenia
• Interventions: Drug: modafinil (M1, M2, M4)

• Registration Number: NCT00711464
• Lead Sponsor: University of California, Los Angeles

Brief Summary

Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This includes many types of cognitive dysfunction, such as in attention, memory and language. These problems 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. Unfortunately, the biochemical aspects of these dysfunctions are presently unknown, and it is not clear whether current psychiatric medications can improve these functions. A recent FDA-approved medication that may improve this function is modafinil. Studies in animals and healthy adults show that this medication can improve many of these cognitive functions. We plan to study the effects of modafinil on these cognitive processes, by giving various doses of this medication to patients before they perform tasks of these cognitive processes. We predict that when patients receive modafinil, they will perform better on a cognitive test, and that these benefits will depend on the dose given.

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 cortex-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 many 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.

This study will evaluate the effects of modafinil on the range of cognitive processes known to be disturbed in schizophrenia. 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 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 the remediation of deficits in cognition in individuals with schizophrenia. We will vary the dose within each participant to evaluate dose-response relationships, and directly compare cognition outcome measures for sensitivity to drug effects.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-07-02
• Study First Submitted QC: 2008-07-07
• Study First Posted: 2008-07-08
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Results First Submitted: 2017-05-03
• Status Verified: 2017-08
• Results First Submitted QC: 2017-08-31
• Last Update Submitted: 2017-08-31
• Results First Posted: 2017-09-29
• Last Update Posted: 2017-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• adults age 18-54
• diagnosis of schizophrenia or schizoaffective disorder, or healthy with no personal or family history of mental illness
• able to provide informed consent

Exclusion Criteria

• history of significant head injury or other neurological illness
• active psychiatric illness requiring significant acute care
• significant intellectual impairment (e.g. standardized full-scale IQ < 70)
• history of medical illness or treatment that is associated with significant increase in risk from modafinil treatment (e.g. cardiac disease)
• significant active substance abuse
• active pregnancy
• active treatment with medications that have drug interactions with modafinil

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
200 mg	modafinil (M1, M2, M4)	modafinil 200 mg oral dose
100 mg	modafinil (M1, M2, M4)	modafinil 100 milligrams oral dose
400 mg	modafinil (M1, M2, M4)	modafinil 400 mg oral dose
Placebo	modafinil (M1, M2, M4)	Single oral placebo capsule

Primary Outcome Measures

Name	Time	Method
Cognitive Performance	3-5 hours	Percent Accuracy on high-control (i.e. difficult) condition on test of cognitive control

Secondary Outcome Measures

Name	Time	Method
Heart Rate	3-5 hours	beats per minute
Systolic Blood Pressure	3-5 hours	systolic blood pressure in mm Hg

Trial Locations

Locations (2)

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

University of California, Davis School of Medicine; 🇺🇸 Sacramento, California, United States