A Dose-Response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients
Information source: University of California, Davis
Information obtained from ClinicalTrials.gov on November 03, 2008 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: modafinil (M1, M2, M4) (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of California, Davis Official(s) and/or principal investigator(s): Michael J. Minzenberg, MD, Principal Investigator, Affiliation: University of California, Davis
Overall contact: Michael J Minzenberg, MD, Phone: 916-734-7174, Email: michael.minzenberg@ucdmc.ucdavis.edu
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
will also enroll healthy adults in these same procedures in order to determine how these
effects are manifest in normal-range cognitive function. We predict that when patients or
control participants receive modafinil, they will perform better on cognitive tests, and that
these benefits will depend on the dose given.
Clinical Details
Official title: A Dose-Response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients.
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Uncontrolled, Single Group Assignment, Efficacy Study
Primary outcome: cognitive performance
Secondary outcome: blood pressureheart rate
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
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. We will vary the dose within each participant to evaluate dose-response
relationships, and directly compare cognition outcome measures for sensitivity to drug
effects.
Eligibility
Minimum age: 18 Years.
Maximum age: 54 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Michael J Minzenberg, MD, Phone: 916-734-7174, Email: michael.minzenberg@ucdmc.ucdavis.edu
University of California, Davis School of Medicine, Sacramento, California 95817, United States; Recruiting Michael J Minzenberg, MD, Principal Investigator
Additional Information
Starting date: May 2008
Ending date: July 2010
Last updated: July 7, 2008
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