Clinical Trial of Dipyridamole in Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This is a 6-week, randomized, double blind, parallel groups designed, olanzapine-controlled trial of oral dipyridamole in symptomatic patients with a (DSM IV) diagnosis of schizophrenia, schizoaffective or schizophreniform disorder. This pilot study aims to provide preliminary estimates of whether the effect sizes of dipyridamole on positive symptoms, negative symptoms, and cognitive deficits differ between schizophrenia patients treated with dipyridamole, and schizophrenia patients treated with olanzapine. A total of 30 subjects will be recruited locally.

Detailed Description
-----------------
Since the demonstrated success of chlorpromazine in treating psychosis in the1950's, the pharmacotherapy of schizophrenia has focused mainly on drugs with antidopaminergic actions. These drugs have robust effects on reality distortion and disorganization symptom complexes, but minimal effect on cognitive impairment, negative symptoms, and functional outcome and quality of life measures. Newer generation antipsychotic drugs have a similar profile of effects, with some advantages on the course of depression, hostility, suicide, hospital readmission rates and motor side effect measures. Side effects such as weight gain, increase in cardiovascular stress and diabetes risk are associated with some new generation drugs. A new class of drugs is needed to address the inadequate effectiveness and the side-effect disadvantages of the currently available pharmacological agents for the treatment of schizophrenia. Recently, new treatment strategies using nicotinergic drugs or agonists at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor have been employed in clinical trials with mixed results. Our proposal focuses on a clinically available adenosine agonist, dipyridamole, in a 6-week clinical trial. Published data suggest effectiveness of dipyridamole in treating psychosis when added to haloperidol treatment. The effectiveness of dipyridamole alone in treating schizophrenia symptoms, although indirectly suggested by several lines of evidence, has not been tested.

Official Title
-----------------
Clinical Trial of Dipyridamole in Schizophrenia

Conditions
-----------------
Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Intervention / Treatment
-----------------
* Drug: Dipyridamole
* Other: Olanzapine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects between ages 18-65, both males and nonpregnant females (on birth control) Diagnosis of schizophrenia, schizoaffective or schizophreniform disorder Ability to give written informed consent Total BPRS score > 27 Psychosis subscale scores > 7 Exclusion Criteria: Patients with coagulative disorders, bleeding diathesis or currently on anticoagulants, and patients with major medical illnesses (including hypertension, angina, and cardiovascular diseases) or an abnormal baseline ECG. Patients with moderate to severe mental retardation. Inability to sign informed consent. Patients with a history of serious violence (e.g., suicide attempts, or assaultive behavior). Patients on clozapine treatment within the 6 weeks leading to the double-blind phase. Patients with a history of olanzapine non-response Positive Urine Toxicology Screen

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Dipyridamole | Drug: Dipyridamole<br>* Week 1- 50 mg bid Week 2- 50 mg am and 100 mg pm Weeks 3-6 100 mg am and 100 mg pm<br>|
| Active Comparator: 2<br>Olanzapine | Other: Olanzapine<br>* Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive Symptoms by Treatment Assignment | The Brief Psychiatric Rating Scale (BPRS) consists of 20 items, with 6 of these items used to assess positive symptom change. The BPRS positive symptom items are: somatic concern, conceptual disorganization, hostility, suspiciousness, hallucinatory behavior, and unusual thought content. Each scale ranges from 1=Not Present to 7=Very Severe. A higher score indicates a more severe positive symptom rating. | Baseline and follow-up | 
| Change in Negative Symptoms by Treatment Assignment | The Scale for the Assessment of Negative Symptoms (SANS) total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, used to measure negative symptoms. Mean SANS total score by treatment and week. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms. | Baseline and Follow-Up | 
| The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160. | Baseline and Follow-Up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia, Positive symptoms, Negative symptoms, Cognitive deficits