Evaluating Isradipine for Cognitive Enhancement in Schizophrenia and Schizoaffective Disorder

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.

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