Modafinil Effects on Cognition in Schizophrenia Patients (InO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00711464
Recruitment Status : Completed
First Posted : July 8, 2008
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
Information provided by (Responsible Party):
Michael Minzenberg, MD, University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: modafinil (M1, M2, M4) Phase 4

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  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Dose-response Study of Modafinil Effects on Cognition in Schizophrenia Patients.
Study Start Date : May 2008
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

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 Name: Provigil

Experimental: 200 mg
modafinil 200 mg oral dose
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil

Experimental: 400 mg
modafinil 400 mg oral dose
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil

Placebo Comparator: Placebo
Single oral placebo capsule
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil

Primary Outcome Measures :
  1. Cognitive Performance [ Time Frame: 3-5 hours ]
    Percent Accuracy on high-control (i.e. difficult) condition on test of cognitive control

Secondary Outcome Measures :
  1. Systolic Blood Pressure [ Time Frame: 3-5 hours ]
    systolic blood pressure in mm Hg

  2. Heart Rate [ Time Frame: 3-5 hours ]
    beats per minute

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 54 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00711464

United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90024
University of California, Davis School of Medicine
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Los Angeles
Principal Investigator: Michael J. Minzenberg, MD University of California, Los Angeles

Responsible Party: Michael Minzenberg, MD, Associate Professor of Clinical Psychiatry, University of California, Davis Identifier: NCT00711464     History of Changes
Other Study ID Numbers: 200715868-1
First Posted: July 8, 2008    Key Record Dates
Results First Posted: September 29, 2017
Last Update Posted: September 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Michael Minzenberg, MD, University of California, Davis:
cognition, pharmacology, memory, attention

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs