A Randomized Double Blind Parallel Trial Administering Methotrexate vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffecive Disorder
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 主要终点
- PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial
研究概览
简要总结
A recent double-blind placebo-controlled study has tested the effect of methotrexate as an add-on treatment for patients with schizophrenia or schizoaffective disorder, administering 10 mg of methotrexate or placebo once a week for a period of three months to 72 patients (Chaudry, Husain et al. 2015). Results showed improvement both in positive symptoms, as measured by the Positive symptoms subscale of the Positive and Negative Syndrome Scale (PANSS), and in total PANSS scores.
The objective of this study is to replicate Chaudry et al.'s study. This proposed study will randomize schizophrenia or schizoaffective disorder patients to methotrexate or placebo for a period of four months.
The study will enroll patients with a DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder confirmed by the Modified Structured Clinical Interview for Diagnosis (SCID). In order to be eligible to enter the study, the patient must have a score of 4 (moderately ill) or greater on the Clinical Global Impression - Severity (CGI-S) scale. In addition, inclusion criteria reflect patients with moderate or more severity on positive symptoms, hence having a score of 4 (moderate) or above on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution. Patients receiving more than one anti-psychotic or depot antipsychotic will be allowed to participate, and patients receiving anti-cholinergic agents, beta-blockers, anti-depressants, mood-stabilizers, sedatives, and anti-anxiety agents will be allowed in the study. Because the clinical status of patients sometimes improves in the days following admission to the hospital, newly hospitalized patients will have their baseline visit 3 days or more after being hospitalized.
详细描述
OBJECTIVES The objective of the study is to evaluate the efficacy of Methotrexate compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia or schizoaffective disorder.
ENDPOINTS Primary outcome measure: PANSS positive score at the end of the trial. Secondary outcome measures: PANSS total, negative and general psychopathology scales, Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I), Social Functioning Scale Assessment (PSP) and rates of drop outs before the end of the trial.
DESIGN Randomized, add-on to anti-psychotics, double blind, placebo-controlled trial.
ASSESSMENTS
- Positive and Negative Syndrome Scale (PANSS). PANSS is a 30-item rating scale widely used in assessment of medication effects in schizophrenia.
- Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I). CGI-S and CGI-I will be used to assess severity of the illness and global improvement.
- The Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale: will be used to assess commonly occurring side effects caused by anti-psychotics.
- The methotrexate toxicity checklist includes rash, oral ulceration, nausea and vomiting, diarrhea, new or increasing dyspnea, new or increasing dry cough, severe sore throat, and abnormal bruising.
- The Personal and Social Performance (PSP) scale will be used to assess social functioning.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-35 years of age, inclusive
- •Females who are abstinent or practicing an established method of birth control (oral contraceptive tablets, hormonal implant device, hormone patch, injectable contraceptive, intrauterine device [IUD]).
- •Willing and able to provide informed consent, after the nature of the study has been fully explained.
- •Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified SCID.
- •Within the first five years of diagnosis.
- •Positive symptoms: 4 (moderate) or above on CGI-S and a score of 4 (moderate) or above on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution.
- •Receiving only one anti-psychotic within PORT dosages
- •Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission
排除标准
- •Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
- •Evidence of significant liver disease. Patients with LFT above normal will be excluded.
- •Pregnant or breast-feeding
- •Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, COPD and other chronic lungs diseases, serious hematological disorder, kidney disease, impaired liver functioning)
- •At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
- •Patients with a current DSM-IV substance or alcohol abuse. Patients with a history of and/or current recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
- •Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
- •Lactose intolerance
- •Immune system disorder or serious infection
- •Patients taking Clozapine
研究组 & 干预措施
Study Drug
Methotrexate 10mg
干预措施: Methotrexate (Drug)
Placebo
Pills equivalent to other study arm (10 mg)
干预措施: Placebo Arm (Other)
结局指标
主要结局
PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial
时间窗: Changes throughout 16 weeks
The positive score subscale has a minimum score of 7 and a maximum score of 49, 7 showing no symptomatology, and 49 showing very severe symptomatology
次要结局
- PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial(Changes throughout 16 weeks)
- PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial(Changes throughout 16 weeks)
- PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial(Changes throughout 16 weeks)
- Rates of drop outs before the end of the trial(Rates throughout 16 weeks)
- Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial(Changes throughout 16 weeks)
- Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial(Changes throughout 16 weeks)
- Social Functioning Scale Assessment (PSP) at the end of the trial(Changes throughout 16 weeks)