A Double-Blind Trial of Adjunctive Valacyclovir to Improve Cognition in Early Phase Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 170
- 试验地点
- 13
- 主要终点
- Working Memory
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
valacyclovir
3000mg daily oral 16 weeks
干预措施: Valacyclovir HCI 500 mg tablets (Drug)
placebo
placebo 6 capsules daily oral 16 weeks
干预措施: placebo (Drug)
结局指标
主要结局
Working Memory
时间窗: Baseline, 8 weeks, and 16 weeks
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.
Visual Memory
时间窗: Baseline, 8 weeks, and 16 weeks
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.
次要结局
- 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)
研究者
Alan Breier
Psychiatrist
Indiana University