Systematic Evaluation of Antiviral Medication in Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to examine whether antiviral medication will help improve psychotic symptoms and cognition in individuals early in the course of schizophrenia or schizoaffective disorder who are exposed to herpes simplex virus, type 1 (HSV 1), a virus that causes commonly occurring and recurrent cold sores.

Detailed Description
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The main objective of the study is to evaluate the efficacy of add-on treatment of Valacyclovir (VAV), an antiviral medication, in the treatment of early course schizophrenia/schizoaffective disorder patients. Our main hypothesis is that the VAV add-on treatment will improve positive, negative and cognitive symptoms in herpes simplex virus (HSV) positive schizophrenia or schizoaffective disorder patients. We hypothesize that the grey matter reductions in specific brain regions (such as prefrontal regions) will improve in patients on VAV + antipsychotic compared to those on placebo + antipsychotic and the improvements in positive, negative and cognitive symptoms will be correlated with the grey matter changes.

Official Title
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A Randomized Double-blind Controlled Trial of Valacyclovir Add-on Treatment of HSV Positive Early Course Schizophrenia Patients

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Valacyclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both genders between the ages of 18-50 years Schizophrenia or schizoaffective disorder as defined in DSM-IV Duration of illness 10 years or less On a stable dose of an antipsychotic medication for at least a month Should score 4 or more on at least one of the subscales of PANSS Positive for HSV1 Written informed consent Exclusion Criteria: Substance abuse in the last month/dependence 6 months prior to the study History of, or current medical/neurological illnesses which affects CNS function e.g., epilepsy, head injury with prolonged loss of consciousness Pregnancy History of immune disorders, HIV infection or currently receiving immunosuppressants Subjects on regular antiviral therapy History of hypersensitivity to Valacyclovir Mental retardation as defined in DSM-IV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valacyclovir<br>1 gram pill taken twice a day for 2 weeks, after 2 weeks it increased to 1.5 gram pill taken twice a day for 16 weeks. | Drug: Valacyclovir<br>* 1 g PO BID x 2 weeks after 2 weeks it goes up to 1.5 g PO BID x 16 weeks along with antipsychotic<br>|
| Placebo Comparator: Sugar pill<br>2 placebo pills taken twice a day for 2 weeks, after 2 weeks 3 pills taken twice a day for 16 weeks. | Drug: Placebo<br>* 2 pills twice a day x 2 weeks, after 2 weeks 3 pills twice a day x 16 weeks along with antipsychotic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS Positive and Negative Syndrome Scale for Schizophrenia | This is a structured measure of severity of psychopathology that includes both positive and negative symptoms. The range is a minimum score of 30 and the maximum is 210. The lower scores suggest milder severity of illness domains. | Baseline, Weeks 2, 4, 6, 10, 14, 18 | 
| Cognitive Function Neuropsychological Battery (Gur Battery) | All results are given as the mean difference between an 18 week follow-up and the baseline battery administrations.This is a computerized test that measures both accuracy and response times. A range for response times is not available because of individual variabilities. Accuracy scores can vary for each test: Working memory accuracy range was 0-16. Verbal memory accuracy range was 0-20. For both, the higher the score the better. No cut offs are available | Baseline, Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Grey Matter Deficit | Gray matter volume changes (in cc) were measured using structural MRI. Changes were reported as gray matter volume in cc. Note: Assessment of blood oxygenation level dependent (BOLD) changes using fMRI were erroneously included in the original study record. | Baseline, Week 18 |