A Double-Blind Trial of Adjunctive Valacyclovir to Improve Cognition in Early Phase Schizophrenia

NCT ID: NCT02008773

Last Updated: 2019-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-26
• Study Completion Date: 2017-06-20

Brief 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.

Detailed Description

One hundred and seventy-five participants (N=70 HSV-1 seropositive and N=105 HSV-1 seronegative) will be randomized 1:1 to receive adjunctive valacyclovir or adjunctive placebo for a 16 week period. The primary outcome that will be assessed is improvement in changes in visual and working memory scores in HSV-1 positive and negative participants over the course of the study. We will also measure the overall cognitive functioning and the severity of psychiatric symptoms over the course of the study and will evaluate the tolerability and safety of valacyclovir treatment in this population. In addition, we will explore the relationship between changes in the levels of inflammatory markers (HSV2, CMV, EBV, CRP, and Toxoplasmosis) and treatment response over the course of the study.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

valacyclovir

3000mg daily oral 16 weeks

Group Type: ACTIVE_COMPARATOR

Valacyclovir HCI 500 mg tablets

Intervention Type: DRUG

Valacyclovir HCI 500 mg capsules 6/day oral for 16 weeks

placebo

placebo 6 capsules daily oral 16 weeks

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo capsules 6/day oral for 16 weeks

Interventions

Valacyclovir HCI 500 mg tablets

Valacyclovir HCI 500 mg capsules 6/day oral for 16 weeks

Intervention Type: DRUG

placebo

placebo capsules 6/day oral for 16 weeks

Intervention Type: DRUG

Other Intervention Names

placebo capsules

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

Sheppard Pratt Health System

OTHER

Sponsor Role: collaborator

University of Maryland

OTHER

Sponsor Role: collaborator

Centers for Behavioral Health, LLC

UNKNOWN

Sponsor Role: collaborator

Laureate Institute for Brain Research, Inc.

OTHER

Sponsor Role: collaborator

University of Kansas Medical Center

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

Innovative Clinical Research, Inc.

INDUSTRY

Sponsor Role: collaborator

University of California Riverside at C.I. Trials, Inc.-Inland Empire

UNKNOWN

Sponsor Role: collaborator

Clinical Innovations

INDUSTRY

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Alan Breier

Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alan Breier, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Faith Dickerson, PhD

Role: PRINCIPAL_INVESTIGATOR

Shepard Pratt Health System

Robert Buchanan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Robert Litman, MD

Role: PRINCIPAL_INVESTIGATOR

Centers for Behavioral Health, LLC

Sheldon Preskorn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas (KUMC)

Brent Wurfel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Laureate Institute for Brain Research

Stephen Marder, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Keith Nuechterlein, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Deepak D'Souza, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Rishi Kakar, MD

Role: PRINCIPAL_INVESTIGATOR

Innovative Clinical Research, Inc.

Gerald Maguire, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Riverside

Diane Highum, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Innovations

Evagelos Coskinas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Clinical Innovations

Locations

C.I. Trials, Inc.-Los Angeles County

Bellflower, California, United States

University of California, Los Angeles

Los Angeles, California, United States

University of California, Riverside at C.I. Trials, Inc.-Inland Empire

Riverside, California, United States

C.I. Trials, Inc.-Orange County

Santa Ana, California, United States

Yale University

New Haven, Connecticut, United States

Innovative Clinical Research, Inc.

Lauderhill, Florida, United States

Prevention and Recovery Center for Early Psychosis

Indianapolis, Indiana, United States

Indiana University Psychotic Disorders Clinic

Indianapolis, Indiana, United States

University of Kansas Medical Center-Witchita

Wichita, Kansas, United States

Maryland Psychiatric Research Center

Baltimore, Maryland, United States

Centers for Behavioral Health, LLC

Rockville, Maryland, United States

Sheppard Pratt Health System

Towson, Maryland, United States

Laureate Institute for Brain Research

Tulsa, Oklahoma, United States

Countries

United States

References

Breier A, Buchanan RW, D'Souza D, Nuechterlein K, Marder S, Dunn W, Preskorn S, Macaluso M, Wurfel B, Maguire G, Kakar R, Highum D, Hoffmeyer D, Coskinas E, Litman R, Vohs JL, Radnovich A, Francis MM, Metzler E, Visco A, Mehdiyoun N, Yang Z, Zhang Y, Yolken RH, Dickerson FB. Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study. Schizophr Res. 2019 Apr;206:291-299. doi: 10.1016/j.schres.2018.11.002. Epub 2018 Nov 23.

Reference Type: DERIVED

PMID: 30478008 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.cbhhealth.com/

Centers for Behavioral Health, LLC

http://www.laureateinstitute.org/

Laureate Institute for Brain Research

http://wichita.kumc.edu/psychiatry-and-behavioral-sciences.html

Kansas University School of Medicine, Psychiatry

Other Identifiers

1310496490

Identifier Type: -

Identifier Source: org_study_id