Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
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
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.
Interventions
DRUGValacyclovir
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
DRUGPlacebo
2 pills twice a day x 2 weeks, after 2 weeks 3 pills twice a day x 16 weeks along with antipsychotic
Sponsors
Stanley Medical Research Institute
Wayne State University
Konasale Prasad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Positive and Negative Syndrome Scale for Schizophrenia | Baseline, Weeks 2, 4, 6, 10, 14, 18 | 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. |
| Cognitive Function Neuropsychological Battery (Gur Battery) | Baseline, Week 18 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Grey Matter Deficit | Baseline, Week 18 | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between 7/2007 and 8/2009 at two separate sites, Pittsburgh and Detroit. Recruitment took place through the local hospital and community mental health and school counseling centers, as well as other research studies and area mental health conferences.
Pre-assignment details
Patients first had a placebo run-in for two weeks along with the psychiatric medications they were on and then randomized at Week 2 to either VAV or placebo group. Enrolled subjects were excluded due to cannabis abuse, claustrophobia, and a duration of illness that was too long.
Participants by arm
| Arm | Count |
|---|---|
| Valacyclovir 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. | 12 |
| Sugar Pill 2 placebo pills taken twice a day for 2 weeks, after 2 weeks 3 pills taken twice a day for 16 weeks. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Sugar Pill | Valacyclovir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Continuous | 28.7 years STANDARD_DEVIATION 8.5 | 29.6 years STANDARD_DEVIATION 9.4 | 29.2 years STANDARD_DEVIATION 8.8 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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
Time frame: Baseline, Week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valacyclovir | Cognitive Function Neuropsychological Battery (Gur Battery) | Working Memory: 2-Back Test Accuracy | 2.13 units on a scale | Standard Deviation 2.68 |
| Valacyclovir | Cognitive Function Neuropsychological Battery (Gur Battery) | Immediate Verbal Memory Reaction Accuracy | 2.44 units on a scale | Standard Deviation 2.62 |
| Sugar Pill | Cognitive Function Neuropsychological Battery (Gur Battery) | Working Memory: 2-Back Test Accuracy | 0.13 units on a scale | Standard Deviation 2.9 |
| Sugar Pill | Cognitive Function Neuropsychological Battery (Gur Battery) | Immediate Verbal Memory Reaction Accuracy | -0.49 units on a scale | Standard Deviation 3.11 |
Primary
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.
Time frame: Baseline, Weeks 2, 4, 6, 10, 14, 18
Population: Comparative analysis of active drug versus placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at the end of the trial | 56.5 Scores on the scale | Standard Deviation 9.289 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at Baseline of the trial | 70.08 Scores on the scale | Standard Deviation 12.616 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 2 of the trial | 72.25 Scores on the scale | Standard Deviation 11.45 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 4 of the trial | 67.36 Scores on the scale | Standard Deviation 12.314 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 6 of the trial | 65.583 Scores on the scale | Standard Deviation 9.228 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 10 of the trial | 65.2 Scores on the scale | Standard Deviation 10.737 |
| Valacyclovir | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 14 of the trial | 57.1 Scores on the scale | Standard Deviation 12.511 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at the end of the trial | 67.125 Scores on the scale | Standard Deviation 13.726 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 6 of the trial | 74.3 Scores on the scale | Standard Deviation 16.275 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at Baseline of the trial | 83.92 Scores on the scale | Standard Deviation 13.895 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 14 of the trial | 69.6 Scores on the scale | Standard Deviation 14.886 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 2 of the trial | 77 Scores on the scale | Standard Deviation 14.917 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 10 of the trial | 73.2 Scores on the scale | Standard Deviation 12.044 |
| Sugar Pill | PANSS Positive and Negative Syndrome Scale for Schizophrenia | Scores at week 4 of the trial | 75.2 Scores on the scale | Standard Deviation 13.998 |
Secondary
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.
Time frame: Baseline, Week 18
Population: Analysis included on all participants on whom baseline and week 18 data were collected. Valacyclovir and placebo groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | Changes in Grey Matter Deficit | 26.83 cm^3 | Standard Deviation 5.04 |
| Sugar Pill | Changes in Grey Matter Deficit | 24.22 cm^3 | Standard Deviation 2.85 |
p-value: 0.004ANCOVA