Psychiatry and
Behavioral Sciences

Schizophrenia Trials

The following studies are currently open to enrollment, and our study coordinator is available to speak with you or your patient(s) about eligibility (click on a study title to read more):

Managing the Metabolic Issues Associated with Second Generation Antipsychotics

Efficacy and Safety of Asenapine Versus Olanzapine in Stable Subjects With Predominant, Persistent Negative Symptoms of Schizophrenia

Combining Two Antipsychotics to Improve Outcome of Schizophrenia

Treatment of Schizophrenia Using a New Antipsychotic

An Open-label Study of Equetro(CBZ-SR) in Outpatients with Aggressive Symptoms and Behavior

Treatment of Adolescents with Schizophrenia

Atypical Antipsychotics Plus Concomitant Mood Stabilizers for Treatment of Schizophrenia or Schizoaffective Disorder

Contact Oxana Ivanova, M.D. at (650) 723-6678, or oivanova@stanford.edu if you are interested in participating in one of these studies.

For further information regarding questions, concerns, or complaints about research, research related injury, and questions about the rights of research participants, please call (650) 723-5244 or call toll free 1-866-680-2906, or write the Administrative Panel on Human Subjects in Medical Research, Administrative Panels Office, Stanford University, Stanford, CA 94305-5401.

Study 1. Managing the Metabolic Issues Associated with Second Generation Antipsychotics

The major concern with new antipsychotics is their tendency to cause weight gain and metabolic side effects. Accordingly, we are part of Foundation for the National Institutes of Health (FNIH)study to treat these problems by switching stabilized patients on risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) to aripiprazole (Abilify) and adding a behavioral intervention to decrease food intake and increase exercise.

The study will include both males and females, 18-65 years old, who are suffering from schizophrenia or schizoaffective disorder and currently taking only one of the following antipsychotic medications: Risperdal, Zyprexa, or Seroquel and having problems with weight and/or cholesterol.

Study 2. Efficacy and Safety of Asenapine Versus Olanzapine in Stable Subjects With Predominant, Persistent Negative Symptoms of Schizophrenia

Asenapine is a new antipsychotic now in Phase III. It is a unique 5-HT2 antagonist, D1 and D2 antagonist, as well as a histamine antagonist.

This study is designed to determine the efficacy and safety of asenapine compared to another, effective atypical antipsychotic – olanzapine. It is an outpatient study in two phases. Phase one starts with a 30-day stable observation period, followed by randomization to either asenapine or olanzapine (in 1:1 ratio), and a 6-month active treatment period. Phase two is a 26-week extension of the Phase one, for patients with a positive response.

The study can include both males and females, 18-65 years old, with predominant, persistent negative symptoms of schizophrenia (lack of emotions, social withdrawal, blank facial expression, lack of social interest, inability to enjoy activities, low motivation, slow movements, lack of interest in life, low energy, decreased activities, difficulty speaking, feeling out of touch), etc.

Study 3. Combining Two Antipsychotics to Improve Outcome of Schizophrenia

There is some anecdotal evidence that combining antipsychotics can improve the outcome of schizophrenia. We are conducting a study to determine if adding aripiprazole (Abilify) to quetiapine (Seroquel) or risperidone (Risperdal) for stabilized patients can improve their response.

The study will last for 16 weeks and include both, male and female, 18 years of age or older with chronic stable schizophrenia or schizoaffective disorder demonstrating an inadequate response to Seroquel or Risperdal.

Study 4. Treatment of Schizophrenia Using a New Antipsychotic

We are continuously examining the effectiveness of new antipsychotics as they come to market. We have been funded to examine the long-term safety, efficacy, and tolerability of a new antipsychotic, bifeprunox. Bifeprunox is a dopamine D2 partial agonist and a serotonin 5-HT1A partial agonist. The study includes open-label treatment with bifeprunox for 52 weeks, including 10 days inpatient.

The study will include both males and females, 18-65 years old, who are suffering from schizophrenia or schizoaffective disorder, relatively stable and in need of treatment.

Study 5. An Open-label Study of Equetro(CBZ-SR) in Outpatients with Aggressive Symptoms and Behavior

An Open-label Study of Equetro(CBZ-SR) in Outpatients with Aggressive Symptoms and Behavior. Although there have been some data suggesting that immediate release carbamazepine (CBZ) may be effective for management of aggressive symptoms or behavior, there are no data on CBZ-SR in patients with schizophrenia who are partially responsive to other psychotropic agents.

The study will include both males and females, 18-65 years old, who are suffering from schizophrenia or schizoaffective disorder and currently being treated with only one antipsychotic medication or mood stabilizer for at least 30 days prior to beginning of the study.

Study 6. Treatment of Adolescents with Schizophrenia

Studies of new antipsychotics in adolescent populations are rare. This study examines treatment of adolescent schizophrenia with Geodon (ziprasidone). Subjects will be males or females between 13-17years of age with diagnosis of schizophrenia being “unstable or partially responsive”. Treatment extends over 6 months.

Study 7. Atypical Antipsychotics Plus Concomitant Mood Stabilizers for Treatment of Schizophrenia or Schizoaffective Disorder

We know that a new generation of antipsychotics can improve the outcome of schizophrenia. However, often there is only a partial response. Accordingly, we will examine whether the addition of a mood stabilizer to an antipsychotic medication will result in an improvement in the symptoms and function after the acute phase. The treatment includes divalproex sodium or lamotrigine as an add-on therapy to a current antipsychotic in a double-blind, placebo-controlled, 4 month study.

The study will include both males and females, 18-65 years old, who are suffering from schizophrenia or schizoaffective disorder and taking only one of the following antipsychotic medications for at least 30 days: risperidone, olanzapine, aripiprazole, clozapine, quetiapine or ziprasidone.


 

The remaining studies on this page are no longer recruiting subjects:

Metabolic Effects of Antipsychotics and Treatment with Aripiprazole

This study focuses on what has become the major concern with the new generation of antipsychotics, i.e. weight gain, which has the potential to increase the risk of cardiovascular complications. The recent introduction of a third generation of antipsychotics, with a different mechanism of action, presents a possible new opportunity for managing this significant side effect.

The study we are conducting will include both males and females, 18-65 years old, who have a diagnosis of schizophrenia or schizoaffective disorder, are moderately to severely overweight, and currently are receiving a stable dose of one or more antipsychotics (clozapine, risperidone, olanzapine, quetiapine or ziprasidone).

After consultation and a workup, we will (with Dr. Reaven's lab) do testing of metabolic parameters, and switch patients to aripiprazole from their current antipsychotic examining weight changes and efficacy of medication.

Treatment of Schizophrenia with OCD Symptoms

The goal of this study is to test the effectiveness of an antipsychotic, aripiprazole, as a monotherapy in patients whose symptoms of schizophrenia are concurrent with symptoms typical of obsessive-compulsive disorder. For non-responders, we will add an antidepressant, citalopram.

To be considered for this study, a patient must be 18 to 65 years old, have a diagnosis of schizophrenia or schizoaffective disorder, and have some symptoms of obsessive-compulsive disorder.

Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) - National Institute Of Mental Health (NIMH) Clinical Trial

A study of up to 23 months comparing the effectiveness of five FDA approved atypicals - Zyprexa, Risperidone, Seroquel, Geodon and Clozapine. Patients between the ages of 18-65 diagnosed with Schizophrenia are eligible to be in the study. They should not have a significant substance use disorder within the last 3 months.

Patients will be evaluated on an outpatient basis for clinical symptoms, medication side effects and other factors. They will receive physical examinations, neurocognitive testing, routine blood work and EKG's at regular intervals throughout the study. Treatment by the Schizophrenia team including medications, lab work and clinic visits are offered free of charge.

The person to contact for information regarding this study is Sudeepthi Prasad at (650) 723-6678, or sprasad@stanford.edu .

Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) Study

An International Multi center Large Simple Trial to compare the cardiovascular safety of Ziprasidone(Geodon) and Olanzapine(Zyprexa).

This is a 52 weeks outpatient study which provides participants with access to either Geodon or Zyprexa at a retail pharmacy. Each patient will receive his/her authorized medication for a period of 1 year from the date the prescription is filled. Treatment by the schizophrenia team, medication and clinic visits are offered free of charge. Schizophrenia clinic also offers support groups for both patients and families free of charge.

The person to contact for information regarding this study is Sudeepthi Prasad at (650) 723-6678, or sprasad@stanford.edu .

Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: A Randomized Double Blind 52 Week Comparison

A one-year study to compare the effectiveness and side effects of three antipsychotic medications (olanzapine, quetiapine, and risperidone) for the treatment of schizophrenia, schizophreniform, or schizoaffective disorder. All of these medications are currently approved by the FDA for use in the United States. We will study the main reasons why study participants stop taking each of the study medications because this problem sometimes is encountered in the treatment of the illness. We will also study the effects of the medications on symptoms and functioning. We will study the side effects of the medications, use of mental health services, and quality of life.

The person to contact for information regarding this study is Rona Hu, M.D. at (650) 723-7041, email: ronahu@stanford.edu

Broad Effectiveness Trial of Aripiprazole (BETA), Dr. Rona Hu

Aripiprazole is considered the first member of the new generation of atypical antipsychotic drugs. It is different from atypical and conventional antipsychotics in that it creates a balance between too much and too little dopamine in the brain. Aripiprazole has undergone a number of studies, showing that it is much better at controlling both the positive and negative symptoms of schizophrenia than placebo (a non-active substance, like a sugar pill). Also, it is equal to haloperidol (Haldol®) and risperidone (Risperdal®) in its ability to control symptoms.

In a study comparing aripiprazole with placebo, the drug effectively managed the symptoms of schizophrenia, but also demonstrated a significantly low incidence of side effects. More importantly, since aripiprazole was well tolerated, few patients stopped treatment.

The recommended starting dose for aripiprazole is 15mg/day, once daily. 30 mg administered once daily has been established as an effective dose and is the highest dose systematically evaluated in clinical trials. Aripiprazole can be taken with or without meals.

Currently, aripiprazole is awaiting Food and Drug Administration (FDA) approval. Psychopharmacology Update 13(2):1, 4-5, 2002. © 2002 Manisses Communications Group, Inc.

Safety and Efficacy of Ziprasidone (Zeldox) and Olanzapine (Zyprexa) in Patients with Schizophrenia or Schizoaffective Disorder Needing Inpatient Care

This project lasts for six weeks with the possibility of participation in a six month outpatient continuation study.

Each patient will begin the study with a 21 day minimum hospitalization period followed by weekly outpatient visits. Each patient will be randomized to either ziprasidone or olanzapine.

Patients will receive physical examinations, neurocognitive testing, routine blood work, and electrocardiograms, at regular intervals throughout the study. The patient may also participate in inpatient therapy groups while in the hospital. Treatment by the schizophrenia team, including hospitalization, medication, lab work, and clinic visits are offered free of charge.The Schizophrenia Clinic also offers supports groups for both patients and t heir families free of charge.

Seroquel vs. I.M. Haldol in the Treatment of Schizophrenia

An outpatient study to determine the quality of maintenance treatment and level of side effects with antipsychotic medication. Persons between the ages of 18 and 60 with schizophrenia or schizoaffective disorder Will receive either Seroquel or Haldol Decanoate for a maximum of two and one half years.

IM Risperidone in the Treatment of Subjects with Schizophrenia

A 14 week study consisting of both inpatient and outpatient treatment. Persons must be between the ages of 18 and 55 and must not suffer from any other psychiatric disorders. Upon completion, patients may choose to continue in a one _year outpatient study.

Quetiapine Vs. Haloperidol Decanoate For The Long _Term Treatment Of Schizophrenia And Schizoaffective Disorder

This is a two year outpatient study, designed to determine whether oral quetiapine (Seroquel ) is better for maintenance treatment of schizophrenia and schizoaffective disorder than depot haloperidol, a standard treatment. The data gathered in this study will help determine whether quetiapine causes fewer side effects, such as stiffness and restlessness, than haloperidol in addition to its potential cost effectiveness. Patients who pass screening evaluation will be randomly assigned to receive either oral Seroquel or depot haloperidol which is administered via monthly injections. Patients will be evaluated monthly, on an outpatient basis, for clinical symptoms, medication side effects, and other factors. Patients will receive physical examinations, routine blood work, and electrocardiograms, at regular intervals throughout the study. Treatment by the schizophrenia team, including medication, lab work, and clinic visits are offered free of charge.

Aripiprazole vs, Olanzapine in the Treatment of Schizophrenia

A 12 week study consisting of both inpatient and outpatient treatment, will compare the safety and tolerability of aripiprazole versus olanzapine as evidenced by weight gain and other measures of adverse events during treatment. Persons must be 18 years of age or older and must not suffer from any other psychiatric disorders. Upon completion, patients may choose to continue in a 40 week outpatient study

Automatic elicitation of cognitive event-related potentials

Background and Aims

The diverse symptoms of schizophrenia have been explained as deficits at both the sensory or input side and at the output side including monitoring thoughts and actions. Deficits in input may include a "defective filter", or gating failure producing sensory overload, cognitive fragmentation and thought disorder. Deficits in output may include misperception of thoughts as hallucinations and one's own actions as being under alien control, as well as the negative symptoms of poverty of thought and action. Event-related potentials (ERP) and functional MRI (fMRI) studies offer new approaches to investi-gate the neural mechanisms underlying these putative mental operations. These approaches include assessment of startle blink modification to assess input deficits and the lateralized readiness potential (LRP) and error related negativity (ERN) components to assess output deficits in response preparation and error monitoring.

On the input side, we have found cortical evidence for pre-pulse inhibition failure in patients with schizophrenia. On the output side, patients with schizophrenia have modestly reduced ERNs on error trials for incorrect responses, and unlike healthy controls, also produce a negative component to correct responses (CRN). They also have a reduced LRP. These scalp-recorded potentials provide evidence of dysfunction in response monitoring and production functions in schizophrenia. Studies of patients with lesions, fMRI studies and dipole analyses of ERPs have implicated the dorsolateral prefrontal cortex (DLPFC) the anterior cingulate cortex (ACC) in processes associated with response monitoring and the basal ganglia in the development and execution of action oriented plans. The relative contribution of these regions to response monitoring is currently the subject of much debate.

Methods

We are conducting ERP studies of schizophrenic patients and age- and gender-matched healthy controls using the ERN, CRN and LRP to test a model of a central monitor involved in seeking matches between the intent to act, stimulus characteristics, and initiation and execution of the response. fMRI data will be collected in parallel paradigms and be combined with ERP data to assess the spatio-temporal dynamics linking particular areas involved in different elements of self-monitoring, both as a normal process, and as a pathophysiological manifestation of schizophrenia. In addition to studying response monitoring, we are also conducting ERP studies of sensory gating that include an attention/task condition in order to assess the relationship between cortical and reflex indicators of gating failures, response moni-toring and symptoms of schizophrenia.

Auditory hallucinations in schizophrenia:

Background and Aims

Auditory hallucinations, the experience of external speech when none is present, are a cardinal symptom of schizophrenia. Recent functional neuroimaging and structural neuroanatomic studies of hallucinations have identified dysfunctions and deficits in the auditory cortex and middle temporal gyrus, centers of the brain involved in language production and comprehension. Further work is needed to amplify these preliminary observations.

Methods

To investigate the phenomon of hallucinations we are using event-related brain potentials (ERPs), a temporally sensitive functional brain imaging tool, to record neural responses to auditory and visual stimuli presented during both naturalistic and mimicked hallucinations. In parallel experiments, we are also using functional magnetic resonance imaging (fMRI) to measure cortical activation. We are measuring ERPs and brain activation during spontaneously occurring hallucinations in patients with schizophrenia and will compare schizophrenics who frequently hallucinate and those who rarely, if ever, do. Among schizophrenics who do hallucinate, we try to compare periods with hallucinations to periods free of them. This will enable us to address the broad question of whether the dysfunction leading to hallucinations is a trait feature of the disease predisposing to hallucinations or whether this dysfunction is more state-like and only present during the actual experience of hallucinations. By comparing hallucinators and nonhallucinators to healthy controls we will establish whether nonhallucinators are more like controls or hallucinating patients in specific brain dysfunctions related to hallucinations.

The design of our project also allows us to investigate brain activation during experimentally similated hallucinations both in normal controls and patients with schizophrenia. Our project involves

  1. Probing Hallucinations. We will probe responsiveness to speech and non-speech sounds of different brain areas serving speech comprehension. We are predicting differential responsiveness to speech and non-speech probes in patients with and without hallucinations. fMRI activation will inform us about the neural substrates of the components of the ERP that are sensitive to hallucinations.
  2. Monitoring Speech. We will assess the hallucinator's ability to monitor the origin of speech by probing the responsiveness of brain areas serving speech comprehension and speech production while subjects are engaged in imagining speech, listening to pre-recorded , or speaking aloud (ERP only).
  3. Our preliminary data on ERPs elicited by speech probes, recorded over left and right temporal lobe sites, showed a significantly different pattern in controls and schizophrenic patients imagining speech in their own voice (self) vs. in a foreign voice (other). In both groups, imagining self speech (i.e., inner speech) involves left temporal lobe structures, however, imagining foreign speech, which is perhaps more akin to a hallucination, results in abnormal involvement of the right temporal lobe in schizophrenics.

These data may explicate the neural dysfunction involved in auditory hallucinations, as well as offer an objective test of the presence of, or the propensity towards, hallucinations.

 

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