A Dose-Response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients - Full Text View

Sponsor:	University of California, Davis
Information provided by:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT00711464

Purpose

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.

Condition	Intervention	Phase
Schizophrenia	Drug: modafinil (M1, M2, M4)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	A Dose-Response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients.

Resource links provided by NLM:

MedlinePlus related topics: Memory Schizophrenia

Drug Information available for: Modafinil

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome Measures:

cognitive performance [ Time Frame: 3-5 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

blood pressure [ Time Frame: 3-5 hours ] [ Designated as safety issue: No ]
heart rate [ Time Frame: 3-5 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	May 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental modafinil 100 milligrams oral dose	Drug: modafinil (M1, M2, M4) modafinil 100, 200, and 400 mg oral dose
2: Experimental modafinil 200 mg oral dose	Drug: modafinil (M1, M2, M4) modafinil 100, 200, and 400 mg oral dose
3: Experimental modafinil 400 mg oral dose	Drug: modafinil (M1, M2, M4) modafinil 100, 200, and 400 mg oral dose

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

Ages Eligible for Study:	18 Years to 54 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711464

Contacts

Contact: Michael J Minzenberg, MD	916-734-7174	michael.minzenberg@ucdmc.ucdavis.edu
Contact: Janeth Nunez-Prado, BA	916-734-3668	janeth.nunez@ucdmc.ucdavis.edu

Locations

United States, California
University of California, Davis School of Medicine	Recruiting
Sacramento, California, United States, 95817
Principal Investigator: Michael J Minzenberg, MD

Sponsors and Collaborators

University of California, Davis

Investigators

Principal Investigator:

Michael J. Minzenberg, MD

University of California, Davis

More Information

No publications provided

Responsible Party:	University of California, Davis School of Medicine ( Michael J. Minzenberg, MD; Assistant Professor )
Study ID Numbers:	200715868-1
Study First Received:	July 2, 2008
Last Updated:	February 18, 2009
ClinicalTrials.gov Identifier:	NCT00711464 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, Davis:

cognition, pharmacology, memory, attention

Additional relevant MeSH terms:

Schizophrenia
Mental Disorders
Therapeutic Uses
Physiological Effects of Drugs
Central Nervous System Stimulants
Protective Agents

Neuroprotective Agents
Central Nervous System Agents
Pharmacologic Actions
Modafinil
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on November 27, 2009