SchizophreniaPhase 4NCT00423943
Modafinil for Treatment of Cognitive Dysfunction in Schizophrenia
A Phase 4 study testing modafinil in people with Schizophrenia and Schizoaffective Disorder, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This appears to be responsible for their difficulties in social and occupational functioning. One particular cognitive function that may be important for schizophrenia is called context processing. Read more about this study
- Who is it for?
- Ages 18 to 54 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- modafinil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Dec 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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 either interferes with experimental measures (e.g. cerebrovascular disease, anemias, etc.) or is associated with significant increase in risk from modafinil treatment (e.g. cardiac disease)
- significant active substance abuse
- presence of ferromagnetic foreign body or prosthesis
- active pregnancy
- active treatment with medications that have drug interactions with modafinil
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Los Angeles School of Medicine
Los Angeles, California, 90095
About this study
Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This appears to be responsible for their difficulties in social and occupational functioning. One particular cognitive function that may be important for schizophrenia is called context processing. This refers to the ability to properly use information in the environment to guide thinking and behavior so that it is appropriate to the present circumstance. Problems with this function 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. This cognitive function depends on a region of the brain called the prefrontal cortex, which shows impaired function in schizophrenia as well. Unfortunately, the biochemical aspects of this dysfunction are presently unknown, and it is not clear whether current psychiatric medications can improve this function. A recent FDA-approved medication that may improve this function is modafinil. Studies in animals and healthy adults show that this medication can improve cognitive functions which are related to context processing. We plan to study the effects of modafinil on context processing and the brain activity that underlies this function. We will use functional MRI and electrophysiology to examine the effects of modafinil, both after a single dose and after sustained (4 week) treatment. We predict that when patients receive modafinil they will perform better on cognitive tests and have improved activity in the regions of the brain that are responsible for these cognitive processes.
Read the 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-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 prefrontal-dependent 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.
Advances in understanding the mechanism of action of these agents will also require the integration of pharmacology with a sophisticated methodology for testing cognition. This goal has been strongly pursued in recent years with the use of functional magnetic resonance imaging (fMRI) to study pharmacological effects on cognition. fMRI studies have identified the cortical network subserving cognitive control and working memory, which are consistently impaired among schizophrenia patients. The study of medication effects on these processes with fMRI (pharmaco-fMRI) will permit the more precise delineation of the cognitive mechanisms amenable to pharmacological intervention.
This study will use fMRI to study the effects of modafinil on the functional neuroanatomy underlying prefrontal cognitive processes. 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 prefrontal 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, both in a single-dose trial and followed by a trial of sustained treatment.
Comparison 1. The effect in healthy adults and adults with schizophrenia/schizoaffective disorder, of Modafinil 200 milligrams single oral dose versus placebo (double-blind, balanced crossover design), on cognitive control task performance, and on activity of dorsolateral prefrontal cortical (DLPFC) during context processing, and anterior cingulate cortex (ACC) during conflict monitoring phases of the task, both measured by fMRI.
Comparison 2. The effect in adults with schizophrenia/schizoaffective disorder, of 4-week randomized, double-blind treatment with Modafinil 200 milligrams daily versus placebo, on cognitive control task performance, and on activity of dorsolateral prefrontal cortical (DLPFC) during context processing, and anterior cingulate cortex (ACC) during conflict monitoring phases of the task, both measured by fMRI.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- modafinil, Placebos
- Keywords
- cognition, memory
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
modafinilDrug
Also called Provigil
200 milligrams daily dose
PlacebosDrug
capsule containing placebo
| Study group | Role | What they receive |
|---|---|---|
| D | Experimental | modafinil Receives: Drug: modafinil |
| Placebo | Placebo comparator | placebo Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Accuracy on High-control (i.e., Difficult) Condition of Preparing to Overcome Prepotency Task
Accuracy change on high-control (i.e., difficult) condition of Preparing to Overcome Prepotency (POP) Task. For high-control condition (red-cue), subjects responded in the incongruent direction (eg, for a right-pointing arrow, press the left button, and vice versa). Increased values indicate improved performance.
Measured: Baseline, 4 weeks
Control-related BOLD Signal Change in Locus Coeruleus
BOLD signal change on high-control (i.e. difficult) condition versus low-control (i.e. easy) condition, on Preparing to Overcome Prepotency Task, measured by fMRI after 4-week treatment.
Measured: 4 weeks
Gamma Power Change in Count of Clusters
Power in Gamma frequency range by scalp electrophysiology after single-dose and after 4-week treatment: Count of Clusters (defined as those with statistically-significant Task-Related Increase, i.e. relatively larger value of wavelet coefficient in wavelet analysis of signal) for high-control (i.e. difficult) condition versus Low-control (i.e. easy) condition, in Oscillatory Power in Time-Frequency Spectrogram. Increased values indicate improved function.
Measured: 4 weeks
Secondary outcomes (2)
Change in Positive Symptoms
Change in Average score (range 0-5) on the Scale for Assessment of Positive Symptoms (SAPS) from baseline to 4 week time-point, ranging from 0 (absent) to 5 (severe). Decreased values indicate improved clinical status (lesser symptom severity).
Measured: Baseline, 4 weeks
Change in Negative Symptoms
Change in average score, ranging from 0 (absent) to 5 (severe), on on Scale for the Assessment of Negative Symptoms (SANS) from baseline to 4-week time-point. Decreased values indicate improved clinical status (lesser symptom severity).
Measured: Baseline, 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2007 (estimated)
- Study startSep 2005
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Minzenberg, MD, University of California, Davis
- Investigators
- Michael J Minzenberg, MD, Principal investigator, University of California, Los AngelesCameron S Carter, MD, Principal investigator, University of California Davis School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00423943
- Sponsor's protocol ID
- 200513585-1
- Status last verified
- Aug 2017
- First submitted
- 16 Jan 2007
- Last updated
- 29 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modafinil for Treatment of Cognitive Dysfunction in Schizophrenia
- ClinicalTrials.gov ID
- NCT00423943
- Acronym / sponsor ID
- 200513585-1
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- cognition, memory
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Jan 2007 (estimated)
- Results
- Posted 29 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This appears to be responsible for their difficulties in social and occupational functioning. One particular cognitive function that may be important for schizophrenia is called context processing. This refers to the ability to properly use information in the environment to guide thinking and behavior so that it is appropriate to the present circumstance. Problems with this function 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. This cognitive function depends on a region of the brain called the prefrontal cortex, which shows impaired function in schizophrenia as well. Unfortunately, the biochemical aspects of this dysfunction are presently unknown, and it is not clear whether current psychiatric medications can improve this function. A recent FDA-approved medication that may improve this function is modafinil. Studies in animals and healthy adults show that this medication can improve cognitive functions which are related to context processing. We plan to study the effects of modafinil on context processing and the brain activity that underlies this function. We will use functional MRI and electrophysiology to examine the effects of modafinil, both after a single dose and after sustained (4 week) treatment. We predict that when patients receive modafinil they will perform better on cognitive tests and have improved activity in the regions of the brain that are responsible for these cognitive processes.
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-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 prefrontal-dependent 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.
Advances in understanding the mechanism of action of these agents will also require the integration of pharmacology with a sophisticated methodology for testing cognition. This goal has been strongly pursued in recent years with the use of functional magnetic resonance imaging (fMRI) to study pharmacological effects on cognition. fMRI studies have identified the cortical network subserving cognitive control and working memory, which are consistently impaired among schizophrenia patients. The study of medication effects on these processes with fMRI (pharmaco-fMRI) will permit the more precise delineation of the cognitive mechanisms amenable to pharmacological intervention.
This study will use fMRI to study the effects of modafinil on the functional neuroanatomy underlying prefrontal cognitive processes. 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 prefrontal 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, both in a single-dose trial and followed by a trial of sustained treatment.
Comparison 1. The effect in healthy adults and adults with schizophrenia/schizoaffective disorder, of Modafinil 200 milligrams single oral dose versus placebo (double-blind, balanced crossover design), on cognitive control task performance, and on activity of dorsolateral prefrontal cortical (DLPFC) during context processing, and anterior cingulate cortex (ACC) during conflict monitoring phases of the task, both measured by fMRI.
Comparison 2. The effect in adults with schizophrenia/schizoaffective disorder, of 4-week randomized, double-blind treatment with Modafinil 200 milligrams daily versus placebo, on cognitive control task performance, and on activity of dorsolateral prefrontal cortical (DLPFC) during context processing, and anterior cingulate cortex (ACC) during conflict monitoring phases of the task, both measured by fMRI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D | Experimental | Drug: modafinilmodafinil |
| Placebo | Placebo comparator | Drug: Placebosplacebo |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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 either interferes with experimental measures (e.g. cerebrovascular disease, anemias, etc.) or is associated with significant increase in risk from modafinil treatment (e.g. cardiac disease)
- significant active substance abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| modafinilAlso: Provigil200 milligrams daily dose | Drug | D |
| Placeboscapsule containing placebo | Drug | Placebo |
Primary outcome
Percent Change in Accuracy on High-control (i.e., Difficult) Condition of Preparing to Overcome Prepotency Task
Time frame: Baseline, 4 weeks
Accuracy change on high-control (i.e., difficult) condition of Preparing to Overcome Prepotency (POP) Task. For high-control condition (red-cue), subjects responded in the incongruent direction (eg, for a right-pointing arrow, press the left button, and vice versa). Increased values indicate improved performance.
Control-related BOLD Signal Change in Locus Coeruleus
Time frame: 4 weeks
BOLD signal change on high-control (i.e. difficult) condition versus low-control (i.e. easy) condition, on Preparing to Overcome Prepotency Task, measured by fMRI after 4-week treatment.
Gamma Power Change in Count of Clusters
Time frame: 4 weeks
Power in Gamma frequency range by scalp electrophysiology after single-dose and after 4-week treatment: Count of Clusters (defined as those with statistically-significant Task-Related Increase, i.e. relatively larger value of wavelet coefficient in wavelet analysis of signal) for high-control (i.e. difficult) condition versus Low-control (i.e. easy) condition, in Oscillatory Power in Time-Frequency Spectrogram. Increased values indicate improved function.
2 secondary outcomes
Change in Positive Symptoms
Time frame: Baseline, 4 weeks
Change in Negative Symptoms
Time frame: Baseline, 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Minzenberg, MD principal investigator
University of California, Los Angeles
Cameron S Carter, MD principal investigator
University of California Davis School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing modafinil in people with Schizophrenia and Schizoaffective Disorder, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Accuracy on High-control (i.e., Difficult) Condition of Preparing to Overcome Prepotency Task (time frame: Baseline, 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017; AzTrials last refreshed its copy on 6 Nov 2026.