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Valacyclovir Augmentation for Cognitive and Functional Remediation in Schizophrenia

Primary Purpose

Herpes Simplex, Schizophrenia, Schizoaffective Disorder

Status
Completed
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Experimental: Valacyclovir treatment
Placebo comparator
Sponsored by
University of Pittsburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Herpes Simplex

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Written informed consent.
  • Both genders, ages 18-50 years
  • Schizophrenia / schizoaffective disorder (DSM IV).
  • Stable dose of antipsychotic for > 1 month, continued throughout the study.
  • Score 4 or more on one or more items of the Positive and Negative Syndrome Scale.
  • Exposed to HSV-1: serum antibody assays.

Exclusion Criteria:

  • Substance abuse in the past month/dependence past 6 months.
  • History / current medical /neurological illnesses e.g., epilepsy.
  • Pregnancy.
  • History of immune disorders, HIV infection, or receiving immune-suppressants.
  • Receiving regular antiviral therapy.
  • History of hypersensitivity to Valacyclovir.
  • Mental retardation as defined in DSM IV.

Sites / Locations

  • Dr. Ram Manohar Lohia Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Valacyclovir treatment

Placebo

Arm Description

Drug: Experimental: Valacyclovir treatment. Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either Valacyclovir (VAV) or placebo (PLA) group in a 1:1 proportion. The VAV group will receive 1.5 g Valacyclovir by mouth, twice daily for 16 weeks, after which they will be followed up without VAV for 4 weeks to monitor delayed adverse effects.

Placebo comparator: Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either VAV or placebo group in a 1:1 proportion. Subjects in the placebo arm will receive placebo for 16 weeks, after which they will be followed up without placebo for 4 weeks to monitor delayed adverse effects.

Outcomes

Primary Outcome Measures

Cognition
The following measures will be used to assess cognitive functioning both before and after treatment with Valacyclovir: Cognition: (1) Trail Making Test (TMT). This paper and pencil test is a convenient estimate of cognitive function, principally focusing on attention, working memory and executive function. (2) Computerized Neuropsychological Battery (CNB). We have validated a Hindi version of the Penn CNB and administered it to over 300 Indian participants. The CNB includes cognitive measures that distinguish SZ cases and relatives from controls. Accuracy and response time are recorded. Cognitive domains assessed: Abstraction and mental flexibility; Attention; Verbal Memory; Face Memory; Spatial Memory; Spatial Processing; Sensory-motor Dexterity; Emotion Processing.

Secondary Outcome Measures

Clinical Severity
Clinical Severity will be measured by the following assessments: (i) Positive and Negative Syndrome Scale (PANSS. The PANSS is 7 point rating scale for 30 psychopathological items based on interviews or reports. (ii) Clinical Global Impression - Severity (CGI-S). The CGI-S is a 7-point scale that rates the severity of the patient's illness at the time of assessment.
Social Function
Social function will be measured by: (1) Independent Living Skills Survey (ILSS), a comprehensive, validated measure of functional living skills including self rated and observer rated portions (2) Sheehan's disability scale (SDS), a self-report tool that assesses functional impairment in work/school, social and family life with a 10-point visual analogue scale; (3) Global Assessment of Function (GAF), a global measure of function and symptom severity (4) Quality of Life Scale (QOL) measures interpersonal, social and occupational functioning.
Side Effects
Side effects will be assessed using: (1) Abnormal Involuntary Movement Scale This scale rates the severity of dyskinetic movements. Orofacial, neck-trunk and distal (limb) movements are rated separately. 2) Barnes Akathisia Scale: A rating scale to assess the severity of drug-induced akathisia.

Full Information

First Posted
February 6, 2013
Last Updated
October 25, 2016
Sponsor
University of Pittsburgh
Collaborators
Dr. Ram Manohar Lohia Hospital, Stanley Medical Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01794897
Brief Title
Valacyclovir Augmentation for Cognitive and Functional Remediation in Schizophrenia
Official Title
Valacyclovir Augmentation for Cognitive and Functional Remediation in Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pittsburgh
Collaborators
Dr. Ram Manohar Lohia Hospital, Stanley Medical Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The effects of Valacyclovir (VAV) augmentation or placebo (PLA) as adjuncts to conventional antipsychotic drug treatment will be evaluated among patients with schizophrenia who have been exposed to herpes simplex virus type 1 (HSV-1). Hypothesis: Valacyclovir (VAV) augmentation improves (a) cognitive and (b) overall function among Herpes Simples Virus 1 (HSV-1) exposed early course schizophrenia patients.
Detailed Description
Design: We propose a randomized double blind placebo controlled study of patients with early course Schizophrenia (SZ) / schizoaffective disorder (SZA) patients exposed to HSV-1, who are receiving antipsychotic drugs. The effects of VAV augmentation or PLA as adjuncts to conventional antipsychotic drug treatment will be evaluated. As outcomes, we will evaluate clinical symptoms, cognitive variables, overall function (including social function) and side effects. The participants will be under the direct care of the Indian investigators during the study. Ratings will be performed blind by research staff. We will pre-screen for HSV-1 exposure. There will be a 2 week placebo run in phase, 16 week augmentation and 4 week follow up to identify post-treatment side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Simplex, Schizophrenia, Schizoaffective Disorder

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Valacyclovir treatment
Arm Type
Experimental
Arm Description
Drug: Experimental: Valacyclovir treatment. Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either Valacyclovir (VAV) or placebo (PLA) group in a 1:1 proportion. The VAV group will receive 1.5 g Valacyclovir by mouth, twice daily for 16 weeks, after which they will be followed up without VAV for 4 weeks to monitor delayed adverse effects.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo comparator: Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either VAV or placebo group in a 1:1 proportion. Subjects in the placebo arm will receive placebo for 16 weeks, after which they will be followed up without placebo for 4 weeks to monitor delayed adverse effects.
Intervention Type
Drug
Intervention Name(s)
Experimental: Valacyclovir treatment
Intervention Description
Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either VAV or placebo group in a 1:1 proportion. The VAV group will receive 1.5 g Valacyclovir by mouth, twice daily for 16 weeks, after which they will be followed up without VAV for 4 weeks to monitor delayed adverse effects.
Intervention Type
Drug
Intervention Name(s)
Placebo comparator
Intervention Description
Patients will have a placebo run-in for two weeks after which they will be evaluated for the variables of interest and then randomized to either VAV or placebo group in a 1:1 proportion. Subjects in the placebo arm will receive placebo for 16 weeks, after which they will be followed up without placebo for 4 weeks to monitor delayed adverse effects.
Primary Outcome Measure Information:
Title
Cognition
Description
The following measures will be used to assess cognitive functioning both before and after treatment with Valacyclovir: Cognition: (1) Trail Making Test (TMT). This paper and pencil test is a convenient estimate of cognitive function, principally focusing on attention, working memory and executive function. (2) Computerized Neuropsychological Battery (CNB). We have validated a Hindi version of the Penn CNB and administered it to over 300 Indian participants. The CNB includes cognitive measures that distinguish SZ cases and relatives from controls. Accuracy and response time are recorded. Cognitive domains assessed: Abstraction and mental flexibility; Attention; Verbal Memory; Face Memory; Spatial Memory; Spatial Processing; Sensory-motor Dexterity; Emotion Processing.
Time Frame
Assessed at week 16
Secondary Outcome Measure Information:
Title
Clinical Severity
Description
Clinical Severity will be measured by the following assessments: (i) Positive and Negative Syndrome Scale (PANSS. The PANSS is 7 point rating scale for 30 psychopathological items based on interviews or reports. (ii) Clinical Global Impression - Severity (CGI-S). The CGI-S is a 7-point scale that rates the severity of the patient's illness at the time of assessment.
Time Frame
Assessed at week 16
Title
Social Function
Description
Social function will be measured by: (1) Independent Living Skills Survey (ILSS), a comprehensive, validated measure of functional living skills including self rated and observer rated portions (2) Sheehan's disability scale (SDS), a self-report tool that assesses functional impairment in work/school, social and family life with a 10-point visual analogue scale; (3) Global Assessment of Function (GAF), a global measure of function and symptom severity (4) Quality of Life Scale (QOL) measures interpersonal, social and occupational functioning.
Time Frame
Assessed at week 16
Title
Side Effects
Description
Side effects will be assessed using: (1) Abnormal Involuntary Movement Scale This scale rates the severity of dyskinetic movements. Orofacial, neck-trunk and distal (limb) movements are rated separately. 2) Barnes Akathisia Scale: A rating scale to assess the severity of drug-induced akathisia.
Time Frame
Assessed at week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent. Both genders, ages 18-50 years Schizophrenia / schizoaffective disorder (DSM IV). Stable dose of antipsychotic for > 1 month, continued throughout the study. Score 4 or more on one or more items of the Positive and Negative Syndrome Scale. Exposed to HSV-1: serum antibody assays. Exclusion Criteria: Substance abuse in the past month/dependence past 6 months. History / current medical /neurological illnesses e.g., epilepsy. Pregnancy. History of immune disorders, HIV infection, or receiving immune-suppressants. Receiving regular antiviral therapy. History of hypersensitivity to Valacyclovir. Mental retardation as defined in DSM IV.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vishwajit Nimgaonkar, MD, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Smita Deshpande, MD
Organizational Affiliation
Dr. Ram Manohar Lohia Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dr. Ram Manohar Lohia Hospital
City
Delhi
Country
India

12. IPD Sharing Statement

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Valacyclovir Augmentation for Cognitive and Functional Remediation in Schizophrenia

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