Allopurinol for Mania: A Randomized Trial Administering Allopurinol vs. Placebo as add-on to Mood Stabilizers and/or Antipsychotics in Patients in a Bipolar Manic Episode.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 24
- 主要终点
- 1) Change from baseline to day 42 in the YMRS
研究概览
简要总结
The objective of the study is to evaluate the efficacy of allopurinol, compared to placebo, as add-on to mood stabilizers and/or antipsychotic in the treatment of patients with bipolar disorder, in a manic episode.
详细描述
An emerging body of evidence supports a role for dysfunctional purinergic related neurotransmission in mood disorders [1, 2]. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists and there is a well characterized antagonistic interaction between adenosine and dopamine receptors in the ventral striatum. Increased adenosynergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. It has been theorized that adenosine may exert some of its antipsychotic effects through modulation of glutamatergic transmission.
Two double-blind, randomized, add-on, placebo-controlled trials comparing allopurinol and placebo in acute mania have showed statistically significant greater improvements in YMRS scores in the allopurinol vs. placebo groups. These empiric data, together with the theoretical and basic science background cited, provide the impetus for this proposed 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-65 years of age, inclusive
- •Only 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]) can be included in the trial.
- •Willing and able to provide informed consent, after the nature of the study has been fully explained
- •Current DSM-IV-TR diagnosis of bipolar I disorder with the current episode manic (296.4x) or mixed (296.6x), as confirmed by the Modified Structured Clinical Interview for DSM-IV (SCID). In order to ensure that this is an acute manic episode, we will verify that the current manic episode was preceded by a period of euthymia or depression. If inpatients, subjects will be included only up to 14 days after admission. Subjects with psychotic features will be included in the study.
- •Patients receiving one or multiple mood stabilizers, and/or one or more anti-psychotics.
- •Inpatients or outpatients.
排除标准
- •Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
- •Pregnant or breast-feeding
- •Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning).
- •Currently taking any of the following medications: warfarin, amoxicilline, ampicilline, theophylline, or mycophenolate mofetil.
- •Likely allergy or sensitivity to Allopurinol
- •At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
- •Suffers from a significant Substance Dependence disorder based on DSM-IV criteria within the 3 months prior to Screening, or is deemed by the Investigator to have a high risk of substance use during the study. Patients with a history of 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 brain trauma.
研究组 & 干预措施
Allopurinol
干预措施: Allopurinol (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
1) Change from baseline to day 42 in the YMRS
时间窗: from baseline to day 42
2) Change from baseline to day 42 in the CGI-BP scale.
时间窗: from baseline to day 42
次要结局
- 1) Change from baseline to day 14 in the YMRS(from baseline to day 14)
- 2) Change from baseline to day 14 in the CGI-BP scale.(from baseline to day 14)
- 3) Change in the PANSS activation subscale score (total score of 6 PANSS items: Hostility, poor impulse control, excitement, uncooperativeness, poor rapport, and tension) from baseline to final assessment (Day 42).(from baseline to day 42)
- 4) Rates of discontinuation in the allopurinol group compared to the placebo group(during the study period (42 days))