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

NCT02008773 | Completed Phase 2 Results DMC

• 1 other identifier: 1310496490
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 13

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.

Conditions

Schizophrenia

Keywords

schizophrenia; schizoaffective; schizophreniform; inflammatory markers; HSV1; cognition; early psychosis; valacyclovir

Outcome Measures

Primary Outcomes (2)

• Visual Memory

  To determine the efficacy of adjunctive valacyclovir, in comparison to placebo, to improve visual memory (Brief Visuospatial Memory Test) in individuals who are HSV-1 positive and early in the course of schizophrenia. The Brief Visuospatial Memory Test is a subscale of the MATRICS Consensus Cognitive Battery (MCCB) and was used to assess visual memory. The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page after being given the opportunity to memorize the figures for 10 seconds. Each page consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the page. A minimum of 0 to 12 points are awarded per trial, so a participant can score between 0 and 36 points for all three trials. The raw score is then converted to a t-score, normed by age and sex. The min and max t-scores are between 0-100, a higher t-score representing a better outcome.

  Baseline, 8 weeks, and 16 weeks

• Working Memory

  Determine the efficacy of adjunctive valacyclovir, in comparison to placebo, on working memory (composite score of the Wechsler Memory Scale-III: Spatial Span and Letter Number Span tests). WMS has 2 sections in which a subject recalls increasingly difficult sequences. The total raw score range for both sections is 0-32. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. LNS consists of 24 increasingly difficult sequences of letters and numbers that a subject is to recall and repeat back in Numeric-Alpha sequential order. The total raw score range is 0-24. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. The Working Memory composite score is calculated by summing the WMS and LNS tscores, a higher tscore reflects better performance.

  Baseline, 8 weeks, and 16 weeks

Secondary Outcomes (4)

• Cognitive Performance

  Baseline, 8 Weeks, and 16 weeks

• Functional Performance

  Baseline, 8 weeks, and 16 weeks

• Psychosis Symptoms

  Baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks

• Functional Performance

  Baseline, 8 weeks, and 16 weeks

Study Arms (2)

valacyclovir

ACTIVE COMPARATOR

3000mg daily oral 16 weeks

Drug: Valacyclovir HCI 500 mg tablets

placebo

PLACEBO COMPARATOR

placebo 6 capsules daily oral 16 weeks

Drug: placebo

Interventions

Valacyclovir HCI 500 mg tablets DRUG

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

valacyclovir

placebo DRUG

placebo capsules 6/day oral for 16 weeks

Also known as: placebo capsules

placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• CGI-S score of less than or equal to 4 (moderately ill) at randomization AND
• 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
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Indiana University: lead
• Stanley Medical Research Institute: collaborator
• Sheppard Pratt Health System: collaborator
• University of Maryland: collaborator
• Centers for Behavioral Health, LLC: collaborator
• Laureate Institute for Brain Research, Inc.: collaborator
• University of Kansas Medical Center: collaborator
• University of California, Los Angeles: collaborator
• Yale University: collaborator
• Innovative Clinical Research, Inc.: collaborator
• University of California Riverside at C.I. Trials, Inc.-Inland Empire: collaborator
• Clinical Innovations: collaborator

Study Sites (13)

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

Bellflower, California, 90706, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

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

Riverside, California, 92506, United States

Location

C.I. Trials, Inc.-Orange County

Santa Ana, California, 92705, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Innovative Clinical Research, Inc.

Lauderhill, Florida, 33319, United States

Location

Prevention and Recovery Center for Early Psychosis

Indianapolis, Indiana, 46202, United States

Location

Indiana University Psychotic Disorders Clinic

Indianapolis, Indiana, 46222, United States

Location

University of Kansas Medical Center-Witchita

Wichita, Kansas, 67214, United States

Location

Maryland Psychiatric Research Center

Baltimore, Maryland, 21228, United States

Location

Centers for Behavioral Health, LLC

Rockville, Maryland, 20850, United States

Location

Sheppard Pratt Health System

Towson, Maryland, 21204, United States

Location

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

Related Publications (1)

• 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.

  PMID: 30478008 DERIVED

Related Links

• Centers for Behavioral Health, LLC
• Laureate Institute for Brain Research
• Kansas University School of Medicine, Psychiatry

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Alan Breier, MD
• Organization: Indiana University Psychotic Disorders Program

abreier@iupui.edu

317-880-8495

Study Officials

• Alan Breier, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Faith Dickerson, PhD

  Shepard Pratt Health System

  PRINCIPAL INVESTIGATOR

• Robert Buchanan, MD

  University of Maryland

  PRINCIPAL INVESTIGATOR

• Robert Litman, MD

  Centers for Behavioral Health, LLC

  PRINCIPAL INVESTIGATOR

• Sheldon Preskorn, MD

  University of Kansas (KUMC)

  PRINCIPAL INVESTIGATOR

• Brent Wurfel, MD, PhD

  Laureate Institute for Brain Research

  PRINCIPAL INVESTIGATOR

• Stephen Marder, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Keith Nuechterlein, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Deepak D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Rishi Kakar, MD

  Innovative Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

• Gerald Maguire, MD

  University of California, Riverside

  PRINCIPAL INVESTIGATOR

• Diane Highum, MD

  Clinical Innovations

  PRINCIPAL INVESTIGATOR

• Evagelos Coskinas, MD, PhD

  Clinical Innovations

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: December 7, 2013
• First Posted: December 11, 2013
• Study Start: March 26, 2014
• Primary Completion: June 20, 2017
• Study Completion: June 20, 2017
• Last Updated: January 30, 2019
• Results First Posted: January 30, 2019

Record last verified: 2019-01

Locations

US (13)