Evaluating Isradipine for Cognitive Enhancement in Schizophrenia and Schizoaffective Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the use of the drug isradipine for cognitive enhancement in patients diagnosed with schizophrenia and schizoaffective disorder.

Detailed Description
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The purpose of this study is to evaluate the use of the drug isradipine for cognitive enhancement in patients diagnosed with schizophrenia and schizoaffective disorder. Incomplete treatment response can be common in these disorders. While there are medications that are effective at treating positive symptoms, some other symptoms of the disorders are often left only partially treated (cognitive impairment and negative symptoms). This study will begin to address if the medication isradipine might help to treat some of the cognitive problems associated with schizophrenia and schizoaffective disorder. Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. It is currently approved by the FDA for hypertension.

Official Title
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A Molecular Approach to Treat Cognition in Schizophrenia: Ca2+ Channel Blockade

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: isradipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 DSM-IV schizophrenia or schizoaffective disorder diagnosis Residual phase of illness criteria met at screen and baseline as defined by item scores of equal to or less than 4 on each of the Brief Psychiatric Rating Scale (BPRS) hallucinatory behavior, unusual thought content, conceptual disorganization items Hamilton Rating Scale for Depression (HRSD) equal to or less than 12 Baseline Clinician Administered Scale for Mania (CARS-M) score of less than 5 Simpson Angus Scale (SAS) total score equal to or less than 6 Treatment with at least one but no more than two stably-dosed second-generation antipsychotic medication (other than clozapine) for equal to or greater than 2 months and no changes planned over the 4-week study period Exclusion Criteria: History of CNS trauma, neurological disorder, ADHD, mental retardation, learning disability, or other non-schizophrenic cause of cognitive impairment DSM-IV diagnosis of substance abuse/dependence within 3 months Pregnant women or women of childbearing age who are not using a medically accepted means of contraception Women who are breastfeeding Active, unstable medical problem that may interfere with cognition Current treatment for hypertension Uncontrolled hypertension Any drug known to interact with isradipine History of GI strictures History of heart disease Abnormal lab or ECG at screen Significant suicidal ideation at baseline (HRSD item 3>2) ECT treatment within 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: isradipine<br>open label | Drug: isradipine<br>* Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel<br>* Other names: Dynacirc CR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MATRICS Consensus Cognitive Battery (MCCB) Change in Neurocognitive/Functional Measures | MATRICS Consensus Cognitive Battery (MCCB) as measure of Neurocognitive/Functional Measures is a standardized battery designed to measure cognitive functioning in people with schizophrenia. The MCCB is represented as a composite T score. A t score is a type of standard score computed by multiplying a z-score (how many standard deviations an element is from the mean) by 10 and adding 50. | baseline and week 4 | 
| UPSA Communication Score | UCSD Performance Skills Assessment (UPSA) - The UPSA is performance-based measure of real-world daily functioning abilities. Participants receive scores for the communication subscale (range = 0-20), with higher score indicating better neurocognitive functioning | baseline and week 4 | 
| Quality of Life (QoL) Scale | The QoL is a measure of the perceived satisfaction in an individual's daily life. This 16-item self-report measure is rated on a 7-point scale, ranging from 1 (terrible) to 7 (delighted), with a total score range from 16-112, where higher scores indicate higher satisfaction with daily life. | baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in PRISE Adverse Event Checklist Score | The PRISE is a physician-administered checklist of adverse events. PRISE contains 33 items, each defined by an adverse event. Each item is rated on a 3-point scale, ranging from 0 (not present) to 2 (distressing), with a total score range from 0-66, where higher scores indicate more adverse events. Mean change for adverse events at week 4 as compared to baseline | up to 4 weeks | 
| Number of Participants With Normal ECG | Number of participants with normal ECG readings to confirm inclusion into study and compared at week 4 to baseline | baseline and week 4 | 
| Number of Participants With Normal Chemistry Panel | Number of participants with normal chemistry panel to confirm inclusion into study at baseline and week | baseline and week 4 | 
| Number of Participants With Normal Complete Blood Count (CBC) | Number of participants with normal CBC to confirm inclusion into study at baseline and week 4 | baseline and week 4 | 
| Abnormal Involuntary Movement Scale (AIMS) | Mean change for abnormal involuntary movements throughout the study. The AIMS is a physician-administered scale of abnormal involuntary movements. AIMS consists of 10 items, each defined by a series of movements. Each item is rated on a 5-point scale, ranging from 0 (not observed) to 4 (severe), with a total score range from 0-40, where higher scores indicate abnormal involuntary movements. | baseline and Week 4 | 
| Modified Simpson Angus Scale (MSAS) | Mean change for drug-induced disordered movement throughout the study. The MSAS is a physician-administered scale of abnormal drug-induced movements. MSAS consists of 6 items, each defined by a series of movements. Each item is rated on a 5-point scale, ranging form 0 (not observed) to 4 (most severe), with a total range of 0-24, where higher scores indicate drug-induced disordered movement. | baseline and week 4 | 
| Beck Scale for Suicidal Ideation (SSI) | a 21-question multiple choice, self-report inventory that is used for measuring the severity of suicidal ideation. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe suicidal ideation symptoms. | up to 4 weeks | 
| Number of Participants With Suicidal Acknowledgments | Number of participants with Suicidal acknowledgements based on the Columbia Suicide Severity Rating Scales (C-SSRS) - Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation). | up to 4 weeks | 
| Number of Participants With a Confirmed SCID-IV | Number of participants with confirm diagnosis for inclusion into study using the Structured Clinical Interview for the DSM-IV (SCID-IV) | baseline | 
| Brief Psychiatric Rating Scale (BPRS) | Mean change for positive symptoms throughout the study. BPRS consists of 18 items, each defined by a series of symptoms. Each item is rated on a 7-point scale, ranging from 1 (not observed) to 7 (very severe), with a total score range from 18-126, where higher scores indicate psychiatric symptoms. | up to 4 weeks | 
| Scale for the Assessment of Negative Symptoms (SANS) | Mean change of negative symptoms throughout the study. SANS consists of 22 items, each defined by a series of symptoms. Each item is rated on a 6-point scale, ranging from 0 (no presence) to 5 (severe presence), with a total range of 0-110, where higher scores indicate negative symptoms. | up to 4 weeks | 
| Hamilton Rating Scale for Depression (HRSD) | Mean change of symptoms of depression throughout the study. HRSD consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where higher score indicates more depressive symptoms | up to 4 weeks | 
| Clinical Global Impression Scale (CGI) | Mean change of clinical impression of severity of psychiatric illness throughout the study. CGI consists of one item, defined by severity of illness. It is rated on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with a total range score of 1-7, where higher score indicates severity of illness. | up to 4 weeks | 
| Clinician Administered Rating Scale for Mania (CARS-M) | Mean change of symptoms of mania throughout the study. CARS-M contains 14 items rated from 0 (absent) to 5 (present) and one item scored 0 to 4, with total range from 0 to 74, where higher score indicates manic symptoms. | up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognition, Schizophrenia, Schizoaffective disorder