A Dose-response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients (InO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Michael Minzenberg, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00711464
First received: July 2, 2008
Last updated: July 5, 2012
Last verified: August 2011
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Dose-response Study of Modafinil Effects on Cognition in Healthy Adults and in Schizophrenia Patients.

Resource links provided by NLM:


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 ]

Enrollment: 40
Study Start Date: May 2008
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
modafinil 100 milligrams oral dose
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil
Experimental: 2
modafinil 200 mg oral dose
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil
Experimental: 3
modafinil 400 mg oral dose
Drug: modafinil (M1, M2, M4)
modafinil 100, 200, and 400 mg oral dose
Other Name: Provigil

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California, Davis School of Medicine
Sacramento, California, United States, 95817
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: Michael Minzenberg, MD, Associate Professor of Clinical Psychiatry, University of California, Davis
ClinicalTrials.gov Identifier: NCT00711464     History of Changes
Other Study ID Numbers: 200715868-1
Study First Received: July 2, 2008
Last Updated: July 5, 2012
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on July 29, 2014