A Double-Blind Trial of Adjunctive Valacyclovir to Improve Cognition in Early Phase Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Valacyclovir HCI 500 mg tablets; placebo
Intervention description: Valacyclovir HCI 500 mg capsules 6/day oral for 16 weeks; placebo capsules 6/day oral for 16 weeks
Intervention MeSH terms: Valacyclovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 170.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: schizophrenia; schizoaffective; schizophreniform; inflammatory markers; HSV1; cognition; early psychosis; valacyclovir

Summary:

      The primary aim of the study is to determine the efficacy of adjunctive valacyclovir, in
      comparison to placebo, to improve visual (Brief Visuospatial Memory Test) and working
      (composite score of the Spatial Span and Letter Number Span tests) memory in individuals who
      are HSV-1 positive and early in the course of schizophrenia.

      We hypothesize that individuals who are HSV-1 positive, but not those who are HSV-1 negative,
      will demonstrate significant valacyclovir efficacy for visual and working memory.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 to 40 years of age at study entry.

          -  Able to give written informed consent.

          -  DSM IV-TR Diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder as
             confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)

          -  Onset of schizophreniform disorder, schizophrenia, or schizoaffective disorder within
             the past eight years as defined by first medical records documentation of these
             conditions

          -  Outpatient or inpatient.

          -  Clinical stability as defined by:

               1. CGI-S score of less than or equal to 4 (moderately ill) at randomization AND

               2. Participants must not have experienced an exacerbation of their illness within 4
                  weeks prior to randomization leading to an intensification of psychiatric care in
                  the opinion of the investigator. Examples of intensification of care include, but
                  are not limited to: inpatient hospitalization, day/partial hospitalization,
                  outpatient crisis management, or psychiatric treatment in an emergency room AND

               3. Antipsychotic treatment stability for at least 4 weeks prior to randomization (no
                  change in antipsychotic dosing, addition of any new antipsychotic medication, or
                  discontinuing an antipsychotic medication)

          -  Fluent in English.

          -  Female participants of childbearing potential must test negative for pregnancy at
             screening visit and agree to use a single, effective, medically acceptable method of
             birth control for the duration of the study.

        Exclusion Criteria:

          -  Known IQ less than 70 as determined by medical history.

          -  IV drug use within previous three month prior to study entry.

          -  Any serious active medical condition that affects brain or cognitive functioning
             (e.g., epilepsy, serious head injury, brain tumor or other neurological disorder) in
             the investigator's opinion.

          -  Known medical history of Human Immunodeficiency Virus (HIV)

          -  Receipt of valacyclovir or chemically-related medication within 2 weeks prior to
             randomization.

          -  History of hypersensitivity to valacyclovir or acyclovir as determined by self-report
             and medical history.

          -  DSM-IV diagnosis of substance dependence within 3 months of study entry (with the
             exception of nicotine or caffeine dependence).

          -  Participants who have participated in a clinical trial with any pharmacological
             treatment intervention for which they received study-related medication in the 4 weeks
             prior to screening AND participants currently receiving treatment (within 1 dosing
             interval plus 4 weeks) with an investigational depot formulation of an antipsychotic
             medication.

          -  Females who are pregnant or planning to become pregnant or breastfeeding or planning
             to do so during the study period.

          -  Participants with current acute, serious, or unstable medical conditions, including,
             but not limited to: inadequately controlled diabetes, asthma, COPD, recent
             cerebrovascular accidents, acute systemic infection or immunologic disease, unstable
             cardiovascular disorders, malnutrition, or hepatic or renal disease, renal including
             renal failure, gastroenterologic, respiratory, endocrinologic, neurologic, hematologic
             including thrombotic thrombocytopenia purpura/hemolytic uremic syndrome, or infectious
             diseases

          -  Participants who require concomitant treatment with any other medication other than
             those allowed as specified in Attachment 2, or with any other medication specifically
             excluded in Attachment 2.

          -  Clinically significant electrocardiogram (ECG) abnormality prior to randomization as
             defined by: participants with a corrected QT interval (Bazett's; QTcB) >450 msec
             (male) or >470 msec (female) prior to randomization. Repeat ECGs will be conducted at
             the discretion of the principal investigator or medical designee.

          -  Test positive for (1) Hepatitis C virus antibody, (2) Hepatitis B surface antigen
             (HBsAg) with or without positive Hepatitis B core total antibody.

          -  Participants with moderate to severe renal impairment as defined by creatinine
             clearance (CrCl) < 60 ml/min (measured by the Cockcroft-Gault equation) at screening.

          -  Participants with hepatic impairment as defined by liver transaminases or total
             bilirubin > 3 × upper limit of normal (ULN).

          -  Participants considered a high risk for suicidal acts - active suicidal ideation as
             determined by clinical interview OR any suicide attempt in 90 days prior to screening.

          -  Participants who demonstrate overtly aggressive behavior or who are deemed to pose a
             homicidal risk in the investigator's opinion.

          -  Participants currently receiving cognitive remediation therapy at time of study entry

          -  Participants who have had electroconvulsive therapy (ECT) within 12 months of study
             entry or who will have ECT at any time during the study.