Systematic Evaluation of Antiviral Medication in Schizophrenia (SEAMS)

• ClinicalTrials.gov Identifier: NCT00514449
• Recruitment Status: Completed
• First Posted: August 10, 2007
• Results First Posted: May 9, 2018
• Last Update Posted: June 14, 2018
• Sponsor: Konasale Prasad
• Collaborators: Stanley Medical Research Institute; Wayne State University
• Information provided by (Responsible Party): Konasale Prasad, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: Valacyclovir; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blind Controlled Trial of Valacyclovir Add-on Treatment of HSV Positive Early Course Schizophrenia Patients
• Study Start Date: June 2007
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Valacyclovir; 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
Placebo Comparator: Sugar pill; 2 placebo pills taken twice a day for 2 weeks, after 2 weeks 3 pills taken twice a day for 16 weeks.	Drug: Placebo; 2 pills twice a day x 2 weeks, after 2 weeks 3 pills twice a day x 16 weeks along with antipsychotic

Outcome Measures

Primary Outcome Measures :

1. PANSS Positive and Negative Syndrome Scale for Schizophrenia [ Time Frame: 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.
2. Cognitive Function Neuropsychological Battery (Gur Battery) [ Time Frame: 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 Outcome Measures :

1. Changes in Grey Matter Deficit [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Michigan

Wayne State University

Detroit, Michigan, United States, 48201

United States, Pennsylvania

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Konasale Prasad

Stanley Medical Research Institute

Wayne State University

Investigators

• Principal Investigator: Konasale Prasad, MD; Western Psychiatric Institute and Clinic
• Principal Investigator: Vishwajit Nimgaonkar, MD, PhD; Western Psychiatric Institute and Clinic
• Principal Investigator: Matcheri Keshavan, MD; Wayne State University
• Principal Investigator: Rajaprabhakaran Rajarethinam, MD; Wayne State University

More Information

Publications:

Prasad KM, Shirts BH, Yolken RH, Keshavan MS, Nimgaonkar VL. Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia. Mol Psychiatry. 2007 Jan;12(1):105-13, 1. Epub 2006 Oct 10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Prasad KM, Eack SM, Keshavan MS, Yolken RH, Iyengar S, Nimgaonkar VL. Antiherpes virus-specific treatment and cognition in schizophrenia: a test-of-concept randomized double-blind placebo-controlled trial. Schizophr Bull. 2013 Jul;39(4):857-66. doi: 10.1093/schbul/sbs040. Epub 2012 Mar 23.

• Responsible Party: Konasale Prasad, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00514449
• Other Study ID Numbers: 0602032
• First Posted: August 10, 2007
• Results First Posted: May 9, 2018
• Last Update Posted: June 14, 2018
• Last Verified: May 2018

Additional relevant MeSH terms:

Schizophrenia; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Valacyclovir; Antiviral Agents; Anti-Infective Agents