Modafinil Effects on Cognition in Schizophrenia Patients (InO)

A Dose-response Study of Modafinil Effects on Cognition in Schizophrenia Patients.

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: modafinil (M1, M2, M4)

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles
    • Sacramento, California, United States, 95817
      • University of California, Davis School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100 mg; modafinil 100 milligrams oral dose	Drug: modafinil (M1, M2, M4); modafinil 100, 200, and 400 mg oral dose; Other Names: Provigil
Experimental: 200 mg; modafinil 200 mg oral dose	Drug: modafinil (M1, M2, M4); modafinil 100, 200, and 400 mg oral dose; Other Names: Provigil
Experimental: 400 mg; modafinil 400 mg oral dose	Drug: modafinil (M1, M2, M4); modafinil 100, 200, and 400 mg oral dose; Other Names: Provigil
Placebo Comparator: Placebo; Single oral placebo capsule	Drug: modafinil (M1, M2, M4); modafinil 100, 200, and 400 mg oral dose; Other Names: Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Performance	Percent Accuracy on high-control (i.e. difficult) condition on test of cognitive control	3-5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	systolic blood pressure in mm Hg	3-5 hours
Heart Rate	beats per minute	3-5 hours

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Michael J. Minzenberg, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: July 2, 2008
• First Submitted That Met QC Criteria: July 7, 2008
• First Posted (Estimate): July 8, 2008

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: cognition, pharmacology, memory, attention
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: 200715868-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No